The co‐chaperone p23 promotes prostate cancer motility and metastasis
Open accessAbstract
Prostate cancer is an androgen receptor (AR)‐dependent malignancy at initiation and progression, therefore hormone therapy is the primary line of systemic treatment. Despite initial disease regression, tumours inevitably recur and progress to an advanced castration‐resistant state a major feature of which is metastasis to the bone. Up‐regulation of AR cofactors and chaperones that overcome low hormone conditions to maintain basal AR activity has been postulated as a mechanism of therapy relapse. p23, an essential component of the apo‐AR complex, acts also after ligand binding to increase AR transcriptional activity and target gene expression, partly by increasing chromatin‐loaded holo‐receptor‐complexes. Immunohistochemical studies have demonstrated increased p23 expression in advanced prostate cancer. Here, we further characterise p23 roles in AR signalling and show that it modulates cytosolic AR levels in the absence of hormone, confirming a chaperoning function in the aporeceptor complex and suggesting p23 upregulates AR signalling at multiple stages. Moreover, p23 protein levels significantly increased upon treatment with not only androgen but also clinically relevant anti‐androgens. This was in contrast to the HSP90 inhibitor 17‐AAG, which did not modulate expression of the cochaperone – important given the HSP90‐independent roles we and others have previously described for p23. Further, we demonstrate p23 is implicated in prostate cancer cell motility and in acquisition of invasiveness capacity through the expression of specific genes known to participate in cancer progression. This may drive metastatic processes in vivo since analysis of prostate tumour biopsies revealed that high nuclear p23 significantly correlated with shorter survival times and with development of metastases in patients with lower grade tumours. We propose that increased p23 expression may allow cells to acquire a more aggressive phenotype, contributing to disease progression, and that p23 is a plausible secondary target in combination with HSP90 inhibition as a potential therapy for advanced prostate cancer.
AI snapshot
Written from the paper’s full text.
TL;DR
p23 stabilizes androgen receptor (AR) in hormone-depleted conditions, is increased by androgen and anti-androgen treatment, and promotes prostate cancer cell motility/invasiveness without affecting growth. High nuclear p23 correlates with shorter survival and metastatic development, especially in lower-grade tumors.
Key findings
- p23 modulates AR protein levels: ectopic p23 prevented AR loss under hormone depletion, while p23 knockdown significantly diminished AR levels at all time points analyzed.
- p23 protein increased after 10 nM mibolerone and 1 μM bicalutamide, but not after 10 nM 17-AAG; 17-AAG decreased AR and increased HSP90 at 72 h.
- p23 did not affect cell growth/viability, but increased migration and invasive potential: p23 knockdown reduced invasion 2.5-fold, and wound recovery at 36 h was ~60% in controls versus ~20% after p23 depletion.
- High nuclear p23 correlated with shorter overall survival (mean 67 to 40.2 months; median 57.4 to 31.7 months; p = 0.017) and shorter disease-specific survival (mean 90.2 to 52.3 months), and with metastasis in Gleason score ≤7 patients.
Methods
- Cell models: LNCaP, C4-2, PC-3, and inducible LNCaP-p23 cells; p23 was overexpressed with doxycycline or knocked down with siRNA, and AR was knocked down with inducible shRNA.
- Assays: Western blotting, qRT-PCR for LAMB1, KYNU, CTSD, and PMP22, transwell migration/invasion, wound healing, and MTS/crystal violet proliferation assays.
- Clinical analysis: immunohistochemistry on tissue microarrays including 321 cancer biopsies and 69 benign biopsies, with nuclear/cytoplasmic p23 scored 0–3 and correlated with survival and metastasis; statistical testing included Student’s t tests and Kaplan–Meier survival analysis.
Limitations
- Stated limitations: Not stated in the paper.
- Evident: the survival analyses use relatively small subsets (n = 53 for overall survival and n = 31 for confirmed metastatic disease), and the clinical data are correlative rather than causal.
- Evident: p23 overexpression did not significantly increase invasion, and the gene-expression analysis focused on selected genes previously identified in breast cancer rather than a global prostate cancer profile.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
Statistics
Claims the paper makes
0 of 41 cited sources checked · 0 supported · 0 flagged
- Findingown data
High nuclear p23 significantly correlates with shorter survival times in patients with lower grade prostate tumours (Gleason score ≤7).
“analysis of prostate tumour biopsies revealed that high nuclear p23 significantly correlated with shorter survival times and with development of metastases in patients with lower grade tumours”
- Also stated in: § Introduction · plain
“nuclear p23 correlates with a decrease in survival in patients with Gleason score ≤7”
Quote in the paperSubstantial claim - Also stated in: § Introduction · plain
- Findingown data
Treatment with synthetic androgen mibolerone (10 nM) significantly increases p23 protein levels in LNCaP cells at and beyond 24 h.
“it caused a significant increase in p23 levels at and beyond 24 h treatment, suggesting p23 protein could be androgen‐stabilised or induced”
- Also stated in: § Abstract · plain
“p23 protein levels significantly increased upon treatment with not only androgen but also clinically relevant anti‐androgens”
Quote in the paperNot a substantial claim - Also stated in: § Abstract · plain
- Findingown data
High nuclear p23 significantly correlates with development of metastases in patients with lower grade prostate tumours.
“analysis of prostate tumour biopsies revealed that high nuclear p23 significantly correlated with shorter survival times and with development of metastases in patients with lower grade tumours”
- Also stated in: § Introduction · plain
“with an increase in metastatic progression”
Quote in the paperSubstantial claim - Also stated in: § Introduction · plain
- Findingown data
Treatment with anti-androgen bicalutamide (1 μM) increases p23 protein levels in LNCaP cells up to 24 h, though less than mibolerone.
“p23 endogenous levels increased over vehicle‐treated up to 24 h after treatment with Bic, although not to the extent seen for Mib, and stayed constant for the remaining duration of the experiment”
- Also stated in: § Abstract · plain
“p23 protein levels significantly increased upon treatment with not only androgen but also clinically relevant anti‐androgens”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
Treatment with HSP90 inhibitor 17-AAG (10 nM) does not significantly affect endogenous p23 protein levels in LNCaP cells.
“did not significantly affect endogenous p23 levels”
- Also stated in: § Abstract · plain
“This was in contrast to the HSP90 inhibitor 17‐AAG, which did not modulate expression of the cochaperone”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
Vinculin was significantly increased (1.4 fold) in cells ectopically expressing p23.
“However vinculin, a component of focal adhesions, was significantly increased (1.4 fold) in cells ectopically expressing p23”
- Also stated in: § Discussion · plain
“ectopic expression of the chaperone enhances vinculin expression”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
Even in patients with confirmed metastatic lesions, there was a significant difference in survival between patients with high and low p23.
“Even in patients with confirmed metastatic lesions, there was a significant difference in survival between patients with high and low p23 (Figure 7B)”
Quote in the paperSubstantial claim - Findingown data
No changes in any of the EMT markers analysed (snail, E-cadherin, vimentin, β-catenin) were observed despite increased V5-p23 expression.
“No changes in any of the markers analysed were observed despite increased V5‐p23 expression”
Quote in the paperSubstantial claim - Findingown data
Reduction in survival was significantly correlated with high p23 nuclear expression.
“reduction in survival was significantly correlated with high p23 nuclear expression”
Quote in the paperSubstantial claim - Findingown data
Altering p23 levels by over-expression or knockdown does not affect prostate cancer cell growth or viability in LNCaP cells.
“over‐expression of p23 (which in the presence of doxycycline was increased by around 60%) did not affect cell growth at any of the time points analysed and no differences were observed when compared to vehicle‐treated cells”
- Also stated in: § Altering p23 levels does not affect prostate cancer cell growth · hedged
“p23 was transiently knocked‐down also indicated no changes in cell viability when compared to the non‐targeting transfected control cells”
Quote in the paperSubstantial claim - Also stated in: § Altering p23 levels does not affect prostate cancer cell growth · hedged
- Findingown data
AR knockdown does not affect p23 protein levels in LNCaP cells.
“AR knockdown had no effect upon p23 protein levels since no differences were observed in DOX‐treated cells compared to those treated with vehicle”
Quote in the paperNot a substantial claim - Findingown data
siRNA knockdown of p23 strongly decreases cell invasion (2.5-fold) in LNCaP cells compared to non-targeting control.
“a strong decrease in cell invasion (2.5‐fold) was seen in cells transfected with siRNA against p23 compared to non‐targeting ‐transfected cells”
Quote in the paperSubstantial claim - Findingown data
Increased ectopic p23 expression significantly increases LNCaP cell migration through an FCS gradient in transwell assays.
“Increased, ectopic expression of p23 significantly increased LNCaP‐p23 cell migration (Figure 5A) through the FCS gradient.”
Quote in the paperSubstantial claim - Findingown data
p23 increases cell motility.
“Figure 6 p23 increases cell motility.”
Quote in the paperSubstantial claim - Findingown data
Patients with high nuclear p23 expression showed significantly shorter overall survival, with mean survival decreasing from 67 to 40.2 months and median from 57.4 to 31.7 months.
“Patients with high nuclear p23 expression showed significantly shorter overall survival, with mean survival decreasing from 67 to 40.2 months and median from 57.4 to 31.7 months (Figure 7A and Table 1, p value = 0.017).”
Quote in the paperSubstantial claim - Findingown data
Depletion of p23 by siRNA in PC3 cells, which do not express functional AR, significantly reduces wound recovery and cell motility.
“We also performed wound healing assays in PC3 cells, which do not express functional AR, and found that depletion of p23 by siRNA also significantly reduced wound recovery i.e. cell motility (Supplemental Figure 1).”
Quote in the paperSubstantial claim - Findingown data
Depleting endogenous p23 in LNCaP cells delays wound recovery in wound-healing assays, with maximal recovery of approximately 20% versus 60% in control cells after 36 h.
“depleting endogenous p23 caused a delay in wound recovery with a maximal recovery of approximately 20%”
- Also stated in: § p23 increases prostate cancer cell motility and invasiveness · plain
“Although progressive wound closure was observed in control cells, which colonised up to 60% of the initial wound area after 36 h”
Quote in the paperSubstantial claim - Also stated in: § p23 increases prostate cancer cell motility and invasiveness · plain
- Findingown data
The survival differences were more significant in patients with lower grade tumours (Gleason grade ≤7).
“The survival differences were more significant in patients with lower grade tumours (Gleason grade ≤7, data not shown).”
Quote in the paperNot a substantial claim - Findingown data
Disease-specific survival was decreased in patients with high nuclear p23, with mean survival decreasing from 90.2 to 52.3 months.
“Disease‐specific survival was also decreased in patients with high nuclear p23, with mean survival decreasing from 90.2 to 52.3 months (Supplemental Figure 2A and Supplemental Table S2).”
Quote in the paperSubstantial claim - Findingown data
No significant differences were observed when analysing p23 cytoplasmic staining.
“No significant differences were observed when analysing p23 cytoplasmic staining”
Quote in the paperSubstantial claim - Findingown data
An inverse correlation between nuclear p23 expression and patient survival was observed.
“An inverse correlation between nuclear p23 expression and patient survival was observed.”
- Also stated in: § Discussion · plain
“analysis of prostate cancer tissue microarrays highlighted a correlation between high nuclear levels of p23 and shorter overall and disease‐specific survival times.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
This occurred in the absence of androgens.
“Importantly, this occurred in the absence of androgens”
Quote in the paperSubstantial claim - Findingown data
Ectopically enhanced expression of p23 resulted in increased AR levels in the absence of hormone.
“Ectopically enhanced expression of p23 resulted in increased AR levels in the absence of hormone”
Quote in the paperSubstantial claim - Findingown data
Transient p23 knockdown significantly increased AR protein turnover.
“Conversely, transient p23 knockdown significantly increased AR protein turnover.”
Quote in the paperSubstantial claim - Findingown data
DOX treatment, i.e. increased p23 expression, significantly altered the expression of several p23-regulated genes.
“We found that DOX treatment, i.e. increased p23 expression, significantly altered the expression of several such genes (Figure 8B)”
Quote in the paperSubstantial claim - Findingown data
Altering p23 levels alone without affecting HSP90 is sufficient to significantly affect AR.
“altering p23 levels alone without affecting the major component of this complex, HSP90, is sufficient to significantly affect AR.”
Quote in the paperSubstantial claim - Findingown data
Modulating levels of p23 protein resulted in changes in AR levels.
“modulating levels of p23 protein resulted in changes in AR levels.”
Quote in the paperSubstantial claim - Findingown data
No effects on prostate cancer cell growth/viability were observed upon manipulation of p23 levels.
“no effects on prostate cancer cell growth/viability were observed upon manipulation of p23 levels.”
Quote in the paperSubstantial claim - Findingown data
High p23 expression in prostate tumours correlated with decreased overall survival in a publicly available transcriptomic dataset.
“analysis of the transcriptomic profiles of a publically available dataset (Taylor et al., 2010) of prostate cancer (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21034) shows high p23 expression in prostate tumours correlated with decreased overall survival (Supplementary Figure S2B).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Taylor et al., 2010
Not checked in the free run.
- Findingown data
p23 over-expression significantly enhanced cell migration.
“In our studies, p23 over‐expression significantly enhanced cell migration”
Quote in the paperSubstantial claim - Interpretationreasoning
p23 upregulates AR signalling at multiple stages.
“suggesting p23 upregulates AR signalling at multiple stages”
- Also stated in: § Effects of androgen upon p23 protein levels · boosted
“Results shown demonstrate p23 can affect AR protein levels, further confirming its role in the signalling pathway.”
Quote in the paperSubstantial claim - Also stated in: § Effects of androgen upon p23 protein levels · boosted
- Premisecitation
p23 is an essential component of the apo-AR complex.
“p23, an essential component of the apo‐AR complex”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Reebye et al., 2012
Not checked in the free run.
- Interpretationreasoning
p23 mediates its effects on prostate cancer cell motility and invasiveness by selectively modulating expression of genes previously involved in metastatic processes.
“we demonstrate p23 is implicated in prostate cancer cell motility and in acquisition of invasiveness capacity through the expression of specific genes known to participate in cancer progression”
- Also stated in: § Introduction · hedged
“p23 may mediate these effects by selectively modulating the expression of genes previously involved in metastatic processes”
Quote in the paperSubstantial claim - Also stated in: § Introduction · hedged
- Interpretationown data
Nuclear p23 has a role in prostate cancer progression.
“further highlighting a role for nuclear p23 in prostate cancer progression.”
Quote in the paperSubstantial claim - Interpretationown data
Endogenous p23 supports invasive potential of prostate cancer cells.
“This supports a role for endogenous p23 in invasive potential of prostate cancer cells.”
Quote in the paperSubstantial claim - Interpretationown data
p23 has no direct role in prostate cancer cell proliferation.
“The results suggest p23 has no direct role in cell proliferation.”
Quote in the paperSubstantial claim - Interpretationown data
p23 could serve as a poor prognostic indicator.
“suggesting p23 could serve as a poor prognostic indicator.”
Quote in the paperSubstantial claim - Interpretationown data
p23 does not exert its effects upon cell motility via changes in EMT markers.
“suggesting p23 does not exert its effects upon cell motility in this manner (Figure 8A).”
Quote in the paperSubstantial claim - Interpretationcitation
It is unlikely that these effects occur at the genomic level.
“It is unlikely that these effects occur at the genomic level given that p23 has not been described to bind any regulatory regions in the vicinity of the AR gene (Massie and Mills, 2011; Sharma et al., 2013) and addition of Mib did not significantly alter p23 gene expression (Supplementary Figure S2).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Massie and Mills, 2011
Not checked in the free run.
- cites Sharma et al., 2013
Not checked in the free run.
- Interpretationown data
p23 is important in stabilising AR in the absence of hormone.
“We now describe that p23 appears to be also important in stabilising AR in the absence of hormone since modulating levels of p23 protein resulted in changes in AR levels.”
Quote in the paperSubstantial claim - Interpretationown data
p23 over-expression causes reprogramming of gene transcription into a potentially more aggressive phenotype.
“suggesting p23 may act by reprogramming gene expression profiles into more aggressive phenotypes.”
- Also stated in: § Discussion · hedged
“over‐expression of p23 is sufficient to cause some reprogramming of gene transcription into a potentially more aggressive phenotype.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · hedged
- Interpretationreasoning
This mimics the situation in prostate cancer patients undergoing androgen deprivation therapy.
“which mimics the situation in prostate cancer patients undergoing androgen deprivation therapy.”
Quote in the paperSubstantial claim - Interpretationown data
p23 has a prominent role in foldosome complex function.
“We have thus demonstrated the prominent role of p23 in foldosome complex function”
Quote in the paperSubstantial claim - Interpretationreasoning
p23 may alter cell motility via modulating the interaction between the plasma membrane and the actin cytoskeleton.
“suggesting p23 may alter cell motility via modulating the interaction between the plasma membrane and the actin cytoskeleton.”
Quote in the paperSubstantial claim - Interpretationown data
The increased AR levels could be due to stabilisation/prevention of degradation of unliganded AR in the cytoplasm.
“which could be due to stabilisation/prevention of degradation of unliganded AR in the cytoplasm.”
Quote in the paperSubstantial claim - Premisecitation
The chaperoning complex is a potentially important therapeutic target in advanced prostate cancer.
“The chaperoning complex is a potentially important therapeutic target in advanced prostate cancer, given the significance of HSP client proteins including growth factors and the AR (Ischia et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Ischia et al., 2013
Not checked in the free run.
- Interpretationown data
p23 could serve as a prognostic indicator to assess the likelihood of developing metastatic lesions in patients with low Gleason stage tumours.
“This data indicates that p23 could serve as a prognostic indicator, to assess the likeliness of developing metastatic lesions in patients with low Gleason stage tumours.”
Quote in the paperSubstantial claim- Rests on an assumption: There is a clinical need to stratify patients with low Gleason stage tumours for metastatic risk as early as possible.
- Interpretationown data
p23 may be implicated in driving prostate cancer progression and metastasis.
“We have provided evidence that p23 may be implicated in driving prostate cancer progression and metastasis”
Quote in the paperSubstantial claim- Rests on an assumption: The in vitro cell motility and invasion assays reflect the metastatic potential of prostate cancer cells in patients.
- Interpretationcitation
p23 is involved in driving tumour cells towards high invasion profiles via modulating EMT-dependent cellular changes and interactions within cytoskeleton components.
“strongly suggesting involvement of p23 in driving tumour cells towards high invasion profiles via modulating some EMT‐dependent cellular changes and interactions within cytoskeleton components.”
Quote in the paperSubstantial claim- Rests on an assumption: Vinculin is implicated in the epithelial to mesenchymal transition (EMT) and tumour spreading.
- Interpretationown data
Our findings confirm a role for p23 as a regulator of events associated with invasion and adhesion in prostate cancer cells.
“our findings confirm a role for p23 as a regulator of events associated with these processes in prostate cancer cells (Oxelmark et al., 2006; Simpson et al., 2010).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Oxelmark et al., 2006
Not checked in the free run.
- cites Simpson et al., 2010
Not checked in the free run.
- Premisecitation
p23−/− MEFs present a vinculin impairment.
“Conversely, p23−/− MEFs present a vinculin impairment (Echtenkamp et al., 2011)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Echtenkamp et al., 2011
Not checked in the free run.
- Interpretationown data
p23 and HSP90 have a role in AR signalling and disease progression involving the acquisition of increased cell motility and invasiveness potential.
“In conclusion, we have provided evidence supporting a role of p23 and HSP90 in AR signalling and disease progression involving the acquisition of increased cell motility and invasiveness potential”
Quote in the paperSubstantial claim- Rests on an assumption: The in vitro cell motility and invasion assays reflect the metastatic potential of prostate cancer cells in patients.
- Interpretationreasoning
p23 is indirectly involved in cell motility and metastatic processes through its role as an HSP90 co-chaperone.
“it is plausible to infer that p23 is also indirectly involved in these processes through its role as an HSP90 co‐chaperone.”
Quote in the paperSubstantial claim- Rests on an assumption: The in vitro cell motility and invasion assays reflect the metastatic potential of prostate cancer cells in patients.
- Interpretationown data
HSP90 and p23 are involved in driving these cellular processes.
“Data presented here suggests HSP90 and p23 are involved in driving these cellular processes”
Quote in the paperSubstantial claim- Rests on an assumption: The in vitro cell motility and invasion assays reflect the metastatic potential of prostate cancer cells in patients.
- May combine two claims. 23
- Classified as probably not a substantial claim. 17
May combine two claims.
Findingown datap23 positively regulates AR protein levels under hormone-depleted conditions, stabilising AR in the absence of hormone.
“Here, we further characterise p23 roles in AR signalling and show that it modulates cytosolic AR levels in the absence of hormone, confirming a chaperoning function in the aporeceptor complex and suggesting p23 upregulates AR signalling at multiple stages.”
- Also stated in: § Altering p23 levels affects AR stabilisation in the absence of ligand · plain
“increasing p23 abrogated this effect and levels of AR remained stable”
- Also stated in: § Altering p23 levels affects AR stabilisation in the absence of ligand · plain
“decreasing p23 significantly diminished AR protein levels for all time points analysed”
Quote in the paperSubstantial claim- Also stated in: § Altering p23 levels affects AR stabilisation in the absence of ligand · plain
May combine two claims.
Findingnone givenHigh p23 expression correlates with decreased survival and bone metastasis in prostate cancer patients.
“High p23 expression correlates with decreased survival and bone metastasis in prostate cancer patients”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataA direct correlation between the development of metastatic lesions and p23 nuclear levels was observed, significant only in patients with Gleason score ≤7.
“In agreement with our in vitro data, a direct correlation between the development of metastatic lesions and p23 nuclear levels was observed although this was only significant in patients with Gleason score ≤7 (Figure 7C).”
- Also stated in: § Discussion · plain
“immunostaining performed on prostate cancer biopsies showed an association between eventual development of metastatic lesions with high nuclear p23 expression in tumours graded Gleason ≤7 at diagnosis.”
Quote in the paperSubstantial claim- Also stated in: § Discussion · plain
May combine two claims.
Findingown datap23 over-expression does not significantly affect cell invasion in LNCaP-p23 cells, although a small increase in invading cells was observed upon DOX treatment.
“p23 over‐expression did not significantly affect cell invasion, although a small increase in the number of invading cells was observed upon DOX treatment”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIncreasing p23 levels did increase invasiveness but this was not significant.
“While increasing p23 levels did increase invasiveness this was not significant”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataReducing p23 levels impacted upon cell proliferation, motility and migration, including reducing motility of AR-negative cells.
“Reducing p23 levels impacted upon cell proliferation, motility and migration, and this included reducing motility of AR‐negative cells.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown datap23 knockdown decreased cell motility and invasiveness potential.
“while p23 knockdown decreased cell motility and invasiveness potential.”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitationp23 acts after ligand binding to increase AR transcriptional activity and target gene expression, partly by increasing chromatin-loaded holo-receptor-complexes.
“p23, an essential component of the apo‐AR complex, acts also after ligand binding to increase AR transcriptional activity and target gene expression, partly by increasing chromatin‐loaded holo‐receptor‐complexes.”
- Also stated in: § Introduction · boosted
“We have previously shown nuclear p23 to enhance AR activity and binding to chromatin, critical steps for AR signalling and prostate cancer development”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Reebye et al., 2012
Not checked in the free run.
- Also stated in: § Introduction · boosted
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitationp23 is up-regulated in several tumour types, including lung, prostate and breast as well as acute lymphoblastic leukaemia.
“it has been shown to be up‐regulated in several tumour types, including lung, prostate and breast as well as acute lymphoblastic leukaemia”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Elmore et al., 2008
Not checked in the free run.
- cites Krebs et al., 2002
Not checked in the free run.
- cites Li et al., 2009
Not checked in the free run.
May combine two claims.
PremisecitationThe interaction between p23 and AR is at least partially HSP90-independent, and a mutant p23 unable to bind HSP90 significantly enhanced AR transcriptional activity similarly to wild type p23.
“Our laboratory has shown that the interaction between p23 and AR is at least partially HSP90‐independent and that a mutant form of p23 unable to bind HSP90 significantly enhanced AR transcriptional activity to a similar extent as observed for wild type p23 (Reebye et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Reebye et al., 2012
Not checked in the free run.
May combine two claims.
Premisecitationp23 expression is increased in advanced prostate cancer and with tumour grade.
“Immunohistochemical studies have demonstrated increased p23 expression in advanced prostate cancer.”
- Also stated in: § Introduction · plain
“to be increased with tumour grade (Reebye et al., 2012)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Reebye et al., 2012
Not checked in the free run.
- Also stated in: § Introduction · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe yeast p23 homologue Sba1 protects cells against the effects of HSP90 inhibitors such as geldanamycin or radicicol.
“the yeast p23 homologue, Sba1, was shown to protect cells against the effects of HSP90 inhibitors such as geldanamycin or radicicol (Forafonov et al., 2008)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Forafonov et al., 2008
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitationp23 enhances cell motility and higher levels correlate with poor prognosis and a reduction in disease-free survival time in breast cancer patients.
“The role of p23 in breast cancer has been extensively studied by the Garabedian laboratory, who showed p23 enhances cell motility and that higher levels correlate with poor prognosis and a reduction in disease‐free survival time in breast cancer patients”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Oxelmark et al., 2006
Not checked in the free run.
- cites Oxelmark et al., 2012
Not checked in the free run.
- cites Oxelmark et al., 2010
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May combine two claims.
Interpretationown dataIncreased p23 expression may allow prostate cancer cells to acquire a more aggressive phenotype, contributing to disease progression.
“We propose that increased p23 expression may allow cells to acquire a more aggressive phenotype, contributing to disease progression”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenp23 expression was scored blindly for epithelial nuclear intensity and number of positive nuclei in each biopsy core.
“p23 expression was scored blindly for epithelial nuclear intensity of staining and number of epithelial nuclei positive per field, in each biopsy core.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataThe effects of p23 on cell motility are mediated via non-AR client proteins, although AR involvement in AR-positive cells is not ruled out.
“This demonstrates that the effects of p23 on cell motility are mediated via non‐AR client proteins, although does not rule out involvement of AR in AR‐positive cells.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataResults are based on three independent experiments.
“Results presented are the mean ± 1 STDEV of three independent experiments.”
- Also stated in: § Effects of androgen upon p23 protein levels · plain
“Results presented are the mean ± 1 standard error of three experiments.”
Quote in the paperNot a substantial claim- Also stated in: § Effects of androgen upon p23 protein levels · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataPositive and negative controls were included in each immunohistochemistry batch.
“Sections known to stain positively were included in each batch, and negative controls were prepared by replacing the primary antibody with TBS buffer.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenIncreased p23 levels cause changes in gene expression associated with invasive malignancies.
“Increased p23 levels cause changes in gene expression associated with invasive malignancies”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationKnocking down p23 reduces vinculin levels.
“supporting previous observations that knocking down p23 reduces vinculin levels (Echtenkamp et al., 2011)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Echtenkamp et al., 2011
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataMigration assays were performed in triplicate.
“Migration assays were performed in triplicate using Companion 24‐well plates and transwell chambers”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitationp23 is important in several cellular processes, including modulating the activity of steroid receptors such as AR, ER, GR and PR.
“Less is known regarding other roles for p23, although it is important in several cellular processes, including modulating the activity of SRs such as AR, ER, GR and PR (Freeman and Yamamoto, 2002; Knoblauch and Garabedian, 1999; Reebye et al., 2012).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Freeman and Yamamoto, 2002
Not checked in the free run.
- cites Knoblauch and Garabedian, 1999
Not checked in the free run.
- cites Reebye et al., 2012
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationLAMB1 encodes a laminin-1 protein shown to have reduced expression in breast cancer.
“LAMB1 encodes a laminin‐1 protein shown to have reduced expression in breast cancer (Minn et al., 2005; Pruitt et al., 2013; Simpson et al., 2010; Tong et al., 2010).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Minn et al., 2005
Not checked in the free run.
- cites Pruitt et al., 2013
Not checked in the free run.
- cites Simpson et al., 2010
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationIn breast cancer cells, p23 modulates the expression of a set of genes dysregulated in advanced breast cancer including those involved in migration, invasion, metabolism or transcriptional regulation.
“Previously Simpson et al. demonstrated that, in breast cancer cells, p23 modulates the expression of a set of genes dysregulated in advanced breast cancer including those involved in migration, invasion, metabolism or transcriptional regulation (Simpson et al., 2012, 2010).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Simpson et al., 2012, 2010
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationKYNU, CTSD and PMP22 are known to be up-regulated in advanced metastatic cancers and correlate with poor prognosis.
“KYNU, CTSD and PMP22 are known to be up‐regulated in advanced metastatic cancers and correlate with poor prognosis”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Minn et al., 2005
Not checked in the free run.
- cites Pruitt et al., 2013
Not checked in the free run.
- cites Simpson et al., 2010
Not checked in the free run.
May combine two claims.
Premiseown datap23 enhances AR transcriptional activity and DNA-binding.
“We previously demonstrated that p23 enhances AR transcriptional activity and DNA‐binding.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitationp23 has been shown to enhance MCF-7 cell invasion and adhesion, potentially facilitating tumour invasion in breast.
“p23 has been already shown to enhance MCF‐7 cell invasion and adhesion, thus potentially facilitating tumour invasion in breast”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Oxelmark et al., 2006
Not checked in the free run.
- cites Simpson et al., 2010
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationHSP90 promotes activation of extra-cellular proteins such as MMP-2, leading to enhanced tumour invasiveness.
“Moreover, HSP90 also promotes activation of extra‐cellular proteins such as MMP‐2, leading to enhanced tumour invasiveness (Eustace et al., 2004; Stellas et al., 2010).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Eustace et al., 2004
Not checked in the free run.
- cites Stellas et al., 2010
Not checked in the free run.
May combine two claims.
Interpretationown dataThe effects of reducing p23 levels are consistent with mediation through other HSP90 client proteins or co-chaperones but do not rule out some contribution of AR.
“This is consistent with the effects being mediated through other HSP90 client proteins or co‐chaperones but does not rule out some contribution of AR, which has previously been described by other groups (Castoria et al., 2011, 2003, 2008).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Castoria et al., 2011
Not checked in the free run.
- cites Castoria et al., 2003
Not checked in the free run.
- cites Castoria et al., 2008
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationHSP90 over-expression enhanced wound recovery.
“HSP90 has also been implicated in cell motility and metastatic processes since HSP90 over‐expression enhanced wound recovery (Tsutsumi and Neckers, 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Tsutsumi and Neckers, 2007
Not checked in the free run.
May combine two claims.
PremisecitationIn a breast cancer model, p23 over-expression neither affected MCF-7 cell growth nor enhanced the expression of growth-related genes, despite increasing transcription of other ER target genes.
“Our results support previous reports by Oxelmark et al. which showed, in a breast cancer model, that p23 over‐expression neither affected MCF‐7 cell growth nor enhanced the expression of growth‐related genes, despite increasing transcription of other ER target genes (Oxelmark et al., 2006).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Oxelmark et al., 2006
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationKnockdown of HSP27 promotes AR degradation through the proteasome pathway while AR mRNA remains unchanged.
“A similar mechanism has been described for HSP27, knockdown of which has been shown to promote AR degradation through the proteasome pathway while AR mRNA remained unchanged (Zoubeidi et al., 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Zoubeidi et al., 2007
Not checked in the free run.
May combine two claims.
Interpretationown datap23 is required but not limiting for the invasion process.
“suggesting that p23 is required but not limiting for this process.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationThe pathway by which p23 acts upon gene expression is conserved across different tissues and cell types, and is not dependent upon AR.
“This is in agreement with previous findings reported in breast cancer cells, suggesting that the pathway by which p23 acts upon gene expression is conserved across different tissues and cell types, and is not dependent upon AR (Echtenkamp et al., 2011; Simpson et al., 2010).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Echtenkamp et al., 2011
Not checked in the free run.
- cites Simpson et al., 2010
Not checked in the free run.
May combine two claims.
Interpretationown dataHigh nuclear p23 is associated with and may drive increased occurrence of metastasis.
“which appears to translate to the clinical scenario whereby high nuclear p23 is associated with and may drive increased occurrence of metastasis.”
Quote in the paperSubstantial claim- Rests on an assumption: There is a clinical need to stratify patients with low Gleason stage tumours for metastatic risk as early as possible.
The paper relies on this without support.
Prostate cancer is an AR-dependent malignancy at initiation and progression, so AR signalling is central to its development and progression.
“Prostate cancer is an androgen receptor (AR)‐dependent malignancy at initiation and progression”
“Prostate cancer is, in its early stages, an AR‐dependent malignancy”
The paper relies on this without support.
Ectopic V5-tagged p23 expressed in the LNCaP-p23 cell line functions similarly to endogenous p23.
“we ectopically expressed V5‐tagged p23 using the LNCaP‐p23 cell line by incubating with 100 nM doxycycline (DOX) for 48 h in full media, to induce ectopic p23 expression”
The paper relies on this without support.
There is a clinical need to stratify patients with low Gleason stage tumours for metastatic risk as early as possible.
“There is a clinical need to stratify such patients for metastatic risk as early as possible, to target aggressive treatment to patients who will benefit and avoid overtreatment of others.”
The paper relies on this without support.
Very little is known about the mechanisms involved in prostate cancer metastasis.
“Although metastasis (usually to the bone) is the most lethal development of prostate cancer, very little is known about the mechanisms involved.”
The paper relies on this without support.
The in vitro cell motility and invasion assays reflect the metastatic potential of prostate cancer cells in patients.
“In agreement with our in vitro data, a direct correlation between the development of metastatic lesions and p23 nuclear levels was observed”
The paper relies on this without support.
Vinculin is implicated in the epithelial to mesenchymal transition (EMT) and tumour spreading.
“which is implicated in the epithelial to mesenchymal transition (EMT) and tumour spreading.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PTGES3 protein is reported to have several protein functions and to be localized to both the cytosol and nucleus.
“PTGES3 protein is reported to have several protein functions and to be localized to both the cytosol and nucleus41–49 (Fig. 3f).”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [42]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Cell-viability reagent is identified as both MTS and MTT
MinorThe proliferation-assay methods specify MTS reagent, while the caption for the same assay specifies MTT reagent.
“Cell viability was assessed by incubation with 20 μl of the MTS reagent (Promega) for 2 h at 37 °C following manufacturer's instructions.”
“Twenty microlitres of MTT reagent was added to each well, incubated for 2 h at 37 °C and absorbance measured at 490 nm at the specified time points.”
Matrigel coating time differs between methods and figure caption
MinorThe transwell-assay methods specify 3 hours of matrigel coating before cell seeding, but the Figure 6 caption specifies 2 hours.
“the top chamber was also pre‐coated with 4 μg/cm2 of matrigel (BD biosciences) for 3 h prior to cell seeding.”
“transwells pre‐coated with collagen for 2 h and matrigel for further 2 h.”
Discussion claims reduced p23 affects proliferation despite reported null result
MinorThe discussion says reducing p23 levels impacted cell proliferation, whereas the results report no change in cell viability after p23 knockdown and conclude that p23 has no direct role in proliferation.
“Reducing p23 levels impacted upon cell proliferation, motility and migration, and this included reducing motility of AR‐negative cells.”
“p23 was transiently knocked‐down also indicated no changes in cell viability when compared to the non‐targeting transfected control cells (Figure 4B). The results suggest p23 has no direct role in cell proliferation.”
Cites
Integrative Genomic Profiling of Human Prostate Cancer
Taylor, B. S., Schultz, N. D., Hieronymus, H., Gopalan, A., Xiao, Y., Carver, B. S., Arora, V. K., Kaushik, P., Cerami, E. G., Reva, B. A., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.05.026 · Cited by 3,653 · see citing works
Genes that mediate breast cancer metastasis to lung
Minn, A. J., Gupta, G. P., Siegel, P. M., Bos, P. D., Shu, W., Giri, D. D., Viale, A., Olshen, A. B., Gerald, W. L., & Massagué, J. (2005) · Nature · doi:10.1038/nature03799 · Cited by 2,922 · cited 1× · see citing works
“KYNU, CTSD and PMP22 are known to be up-regulated in advanced metastatic cancers and correlate with poor prognosis whereas LAMB1 encodes a laminin-1 protein shown to have reduced expression in breast cancer (Minn et al., 2005; Pruitt et al., 2012; Simpson et al., 2010; Tong et al., 2010).”
BackgroundCrystal structure of an Hsp90–nucleotide–p23/Sba1 closed chaperone complex
Ali, M. M. U., Roe, S. M., Vaughan, C. K., Meyer, P., Panaretou, B., Piper, P. W., Prodromou, C., & Pearl, L. H. (2006) · Nature · doi:10.1038/nature04716 · Cited by 962 · cited 2× · see citing works
“…divided into two domains, an aminoterminal region containing an HSP90 binding site (residues 86e108) and an unstructured carboxyl terminal domain (Ali et al., 2006; Martinez-Yamout et al., 2006; Weikl et al., 1999; Zhu and Tytgat, 2004). p23 is the smallest component of the HSP90 chaperone…”
BackgroundHsp90 Molecular Chaperone Inhibitors: Are We There Yet?
Neckers, L., & Workman, P. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1000 · Cited by 960 · cited 1× · see citing works
“We also investigated the effects on p23 protein levels after inhibiting either AR (using the therapeutic anti-androgen bicalutamide (Bic)) or the HSP90-p23 interaction (using the HSP90 inhibitor 17-AAG, currently in phase II clinical trials (Neckers and Workman, 2012)).”
MethodTanioka, T., Nakatani, Y., Semmyo, N., Murakami, M., & Kudo, I. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003504200 · Cited by 708 · cited 1× · see citing works
“…and p23 has also been shown to possess prostaglandin E2 synthase activity, although the significance of this remains unclear since p23 knockout mice do not exhibit impaired prostaglandin enzymatic activity (Felts and Toft, 2003; Grad et al., 2006; Lovgren et al., 2007; Tanioka et al., 2000).”
BackgroundEustace, B. K., Sakurai, T., Stewart, J. K., Yimlamai, D., Unger, C., Zehetmeier, C., Lain, B., Torella, C., Henning, S. W., Beste, G., et al. (2004) · Nature Cell Biology · doi:10.1038/ncb1131 · Cited by 590 · cited 2× · see citing works
“Moreover, HSP90 also promotes activation of extra-cellular proteins such as MMP-2, leading to enhanced tumour invasiveness (Eustace et al., 2004; Stellas et al., 2010).”
BackgroundFunctional requirement of p23 and Hsp90 in telomerase complexesPreprint
Holt, S. E., Aisner, D. L., Baur, J. A., Tesmer, V. M., Dy, M., Ouellette, M., Trager, J. B., Morin, G. B., Toft, D. O., Shay, J. W., et al. (1999) · Genes & Development · doi:10.1101/gad.13.7.817 · Cited by 533 · cited 2× · see citing works
“…the ATP-bound form of HSP90, inhibiting its intrinsic hydrolytic activity and stabilising several HSP90-substrate complexes including Fes tyrosine kinase, transcription factors such as HSF1, telomerase and the reverse transcriptase enzyme (Holt et al., 1999; Hu et al., 2002; Nair et al., 1996).”
BackgroundSharma, N. L., Massie, C. E., Ramos‐Montoya, A., Zecchini, V. R., Scott, H. E., Lamb, A. D. G., MacArthur, S., Stark, R., Warren, A. Y., Mills, I. G., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.11.010 · Cited by 401 · see citing works
Disassembly of Transcriptional Regulatory Complexes by Molecular Chaperones
Freeman, B. C., & Yamamoto, K. R. (2002) · Science · doi:10.1126/science.1073051 · Cited by 400 · see citing works
Chaperone Function of Hsp90-Associated Proteins
Bose, S., Weikl, T., Bügl, H., & Buchner, J. (1996) · Science · doi:10.1126/science.274.5293.1715 · Cited by 379 · cited 1× · see citing works
“…proteins that have been released from HSP90 and p23 has also been shown to possess a passive, ATP-independent chaperoning activity in the C-terminus and suppress the aggregation of denatured proteins (Bose et al., 1996; Freeman et al., 2000, 1996; Freeman and Yamamoto, 2002; Reebye et al., 2012).”
BackgroundFreeman, B. C., Toft, D. O., & Morimoto, R. I. (1996) · Science · doi:10.1126/science.274.5293.1718 · Cited by 370 · cited 1× · see citing works
“…proteins that have been released from HSP90 and p23 has also been shown to possess a passive, ATP-independent chaperoning activity in the C-terminus and suppress the aggregation of denatured proteins (Bose et al., 1996; Freeman et al., 2000, 1996; Freeman and Yamamoto, 2002; Reebye et al., 2012).”
BackgroundAndrogen receptor is a tumor suppressor and proliferator in prostate cancer
Niu, Y., Altuwaijri, S., Lai, K., Wu, C., Ricke, W. A., Messing, E. M., Yao, J. L., Yeh, S., & Chang, C. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804700105 · Cited by 258 · cited 1× · see citing works
“This is consistent with the effects being mediated through other HSP90 client proteins or co-chaperones but does not rule out some contribution of AR, which has previously been described by other groups (Castoria et al., 2011; Castoria et al., 2003; Niu et al., 2008).”
Zoubeidi, A., Zardan, A., Beraldi, E., Fazli, L., Sowery, R. D., Rennie, P. S., Nelson, C. C., & Gleave, M. E. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2057 · Cited by 256 · cited 1× · see citing works
“A similar mechanism has been described for HSP27, knockdown of which has been shown to promote AR degradation through the proteasome pathway while AR mRNA remained unchanged (Zoubeidi et al., 2007).”
BackgroundTsutsumi, S., & Neckers, L. (2007) · Cancer Science · doi:10.1111/j.1349-7006.2007.00561.x · Cited by 239 · see citing works
Extracellular Roles for the Molecular Chaperone, HSP90
Eustace, B. K., & Jay, D. G. (2004) · Cell Cycle · doi:10.4161/cc.3.9.1088 · Cited by 160 · cited 1× · see citing works
“Given the interactions between p23 and HSP90 and the fact that p23 as well as HSP90 has been found in conditioned media of fibrosarcoma cells (Eustace and Jay, 2004), it is plausible to infer that p23 is also indirectly involved in these processes through its role as an HSP90 cochaperone.”
BackgroundRanea, J. A. G., Mirey, G., Camonis, J., & Valencia, A. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)03321-5 · Cited by 144 · cited 2× · see citing works
“INTRODUCTION The molecular chaperone p23 is ubiquitously expressed and highly conserved from yeast to humans(Felts and Toft, 2003; Garcia-Ranea et al., 2002).”
BackgroundCastoria, G., Lombardi, M., Barone, M. V., Bilancio, A., Domenico, M. D., Bottero, D., Vitale, F., Migliaccio, A., & Auricchio, F. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211099 · Cited by 136 · see citing works
Stellas, D., Hamidieh, A. E., & Patsavoudi, E. (2010) · BMC Cell Biology · doi:10.1186/1471-2121-11-51 · Cited by 132 · cited 2× · see citing works
“Moreover, HSP90 also promotes activation of extra-cellular proteins such as MMP-2, leading to enhanced tumour invasiveness (Eustace et al., 2004; Stellas et al., 2010).”
BackgroundRegulation of the androgen receptor by SET9-mediated methylation.
Gaughan, L., Stockley, J., Wang, N., McCracken, S. R. C., Treumann, A., Armstrong, K., Shaheen, F., Watt, K., McEwan, I. J., Wang, C., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq861 · Cited by 127 · cited 1× · see citing works
“Immunohistochemistry was performed using 3 tissue microarrays (TMAs) of benign and malignant prostate biopsies derived from transrectal biopsy, transurethral resection, and radical prostatectomy as previously described (Brooke et al., 2011; Gaughan et al., 2011).”
MethodSelf-citationCheng, H., Snoek, R., Ghaidi, F., Cox, M., & Rennie, P. S. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0028 · Cited by 127 · cited 2× · see citing works
“To further clarify the involvement of androgens and their receptor in p23 regulation, the LNCaP-AR-shRNA cell line, in which AR knockdown is induced upon DOX treatment (Cheng et al., 2006), was used to study the effects of AR on p23 expression.”
MethodRole for Hsp90-Associated Cochaperone p23 in Estrogen Receptor Signal Transduction
Knoblauch, R., & Garabedian, M. J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3748 · Cited by 126 · cited 2× · see citing works
“Less is known regarding other roles for p23, although it is important in several cellular processes, including modulating the activity of SRs such as AR, ER, GR and PR (Freeman and Yamamoto, 2002; Knoblauch and Garabedian, 1999; Reebye et al., 2012).”
BackgroundHutchison, K. A., Stancato, L. F., Owens-Grillo, J. K., Johnson, J. L., Krishna, P., Toft, D. O., & Pratt, W. B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.32.18841 · Cited by 125 · cited 1× · see citing works
“…as a component of the progesterone receptor (PR) complex but is an intrinsic component of several other steroid receptor (SR) hetero-complexes, exerting distinct effects on different receptors (Freeman and Yamamoto, 2002; Hutchison et al., 1995; Nair et al., 1996; Reebye et al., 2012).”
Backgroundp23, a simple protein with complex activities
Felts, S. J., & Toft, D. O. (2003) · Cell Stress and Chaperones · doi:10.1379/1466-1268(2003)008 · Cited by 116 · see citing works
Hu, J., Toft, D. O., Anselmo, D., & Wang, X. (2002) · Journal of Virology · doi:10.1128/jvi.76.1.269-279.2002 · Cited by 106 · cited 1× · see citing works
“p23 is the smallest component of the HSP90 chaperone machinery, with a molecular weight of 23,000 Da, and is mainly known for binding the ATP-bound form of HSP90, inhibiting its intrinsic hydrolytic activity and stabilising several HSP90-substrate complexes including Fes tyrosine kinase, transcription factors such as…”
BackgroundAndrogen-Induced Cell Migration: Role of Androgen Receptor/Filamin A Association
Castoria, G., D’Amato, L., Ciociola, A., Giovannelli, P., Giraldi, T., Sepe, L., Paolella, G., Barone, M. V., Migliaccio, A., & Auricchio, F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017218 · Cited by 102 · see citing works
Weikl, T., Abelmann, K., & Buchner, J. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3172 · Cited by 97 · cited 1× · see citing works
“…containing an HSP90 binding site (residues 86e108) and an unstructured carboxyl terminal domain (Ali et al., 2006; Martinez-Yamout et al., 2006; Weikl et al., 1999; Zhu and Tytgat, 2004). p23 is the smallest component of the HSP90 chaperone machinery, with a molecular weight of 23,000 Da, and…”
BackgroundThe Hsp90 Cochaperone p23 Is Essential for Perinatal Survival
Grad, I., McKee, T., Ludwig, S. M., Hoyle, G. W., Ruíz, P., Wurst, W., Floß, T., Miller, C. A., & Picard, D. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00734-06 · Cited by 91 · cited 1× · see citing works
“…and p23 has also been shown to possess prostaglandin E2 synthase activity, although the significance of this remains unclear since p23 knockout mice do not exhibit impaired prostaglandin enzymatic activity (Felts and Toft, 2003; Grad et al., 2006; Lovgren et al., 2007; Tanioka et al., 2000).”
BackgroundGlobal Functional Map of the p23 Molecular Chaperone Reveals an Extensive Cellular Network
Echtenkamp, F., Zelin, E., Oxelmark, E., Woo, J. I., Andrews, B., Garabedian, M. J., & Freeman, B. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.05.029 · Cited by 89 · cited 3× · see citing works
“This is in agreement with previous findings reported in breast cancer cells, suggesting that the pathway by which p23 acts upon gene expression is conserved across different tissues and cell types, and is not dependent upon AR (Echtenkamp et al., 2011; Simpson et al., 2010).”
BackgroundResultInfluentialp23/Sba1p protects against Hsp90 inhibitors independently of its intrinsic chaperone activity
Forafonov, F., Toogun, O. A., Grad, I., Suslova, E., Freeman, B. C., & Picard, D. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.02246-07 · Cited by 84 · cited 1× · see citing works
“However, the yeast p23 homologue, Sba1, was shown to protect cells against the effects of HSP90 inhibitors such as geldanamycin or radicicol (Forafonov et al., 2008) and here we show that both androgen and antiandrogens can increase p23 protein levels.”
BackgroundLovgren, A. K., Kovářová, M., & Koller, B. H. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02314-06 · Cited by 81 · cited 1× · see citing works
“…and p23 has also been shown to possess prostaglandin E2 synthase activity, although the significance of this remains unclear since p23 knockout mice do not exhibit impaired prostaglandin enzymatic activity (Felts and Toft, 2003; Grad et al., 2006; Lovgren et al., 2007; Tanioka et al., 2000).”
BackgroundFUS/TLS Is a Novel Mediator of Androgen-Dependent Cell-Cycle Progression and Prostate Cancer Growth
Brooke, G. N., Culley, R. L., Dart, D. A., Mann, D. J., Gaughan, L., McCracken, S. R., Robson, C. N., Spencer‐Dene, B., Gamble, S. C., Powell, S. M., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0874 · Cited by 79 · cited 1× · see citing works
“8 Immunohistochemistry was performed using 3 tissue microarrays (TMAs) of benign and malignant prostate biopsies derived from transrectal biopsy, transurethral resection, and radical prostatectomy as previously described(Brooke et al., 2011; Gaughan et al., 2011).”
MethodSelf-citationLocalization of Sites of Interaction between p23 and Hsp90 in Solution
Martinez‐Yamout, M. A., Venkitakrishnan, R. P., Preece, N. E., Kroon, G. J. A., Wright, P. E., & Dyson, H. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601759200 · Cited by 66 · cited 1× · see citing works
“…domains, an aminoterminal region containing an HSP90 binding site (residues 86e108) and an unstructured carboxyl terminal domain (Ali et al., 2006; Martinez-Yamout et al., 2006; Weikl et al., 1999; Zhu and Tytgat, 2004). p23 is the smallest component of the HSP90 chaperone machinery, with a…”
BackgroundLamoureux, F., Thomas, C., Yin, M., Kuruma, H., Fazli, L., Gleave, M., & Zoubeidi, A. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3077 · Cited by 63 · cited 1× · see citing works
“Increased HSP90 levels following treatment with an HSP90 inhibitor has previously been reported, and attributed to cellular stress response following HSP90 inhibition (Lamoureux et al., 2011).”
BackgroundALG-2: a Ca2+-binding modulator protein involved in cell proliferation and in cell death
Krebs, J. J. R., Saremaslani, P., & Caduff, R. F. (2002) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/s1570-9639(02)00446-6 · Cited by 58 · cited 2× · see citing works
“…processes as it has been shown to be upregulated in several tumour types, including lung, prostate and breast as well as acute lymphoblastic leukaemia (Elmore et al., 2008; Krebs et al., 2002; Li et al., 2009; Liu et al., 2012; Mollerup et al., 2003; Oxelmark et al., 2006; Reebye et al., 2012).”
BackgroundOxelmark, E., Roth, J., Brooks, P., Braunstein, S., Schneider, R., & Garabedian, M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00009-06 · Cited by 53 · cited 6× · see citing works
“…of p23 in breast cancer has been extensively studied by the Garabedian laboratory, who showed p23 enhances cell motility and that higher levels correlate with poor prognosis and a reduction in disease-free survival time in breast cancer patients (Oxelmark et al., 2006; Simpson et al., 2012, 2010).”
BackgroundResultInfluentialSpring, J. H. (2002) · Cited by 48 · see citing works
Reebye, V., Querol Cano, L., Lavery, D. N., Brooke, G. N., Powell, S. M., Chotai, D., Walker, M. M., Whitaker, H. C., Wait, R., Hurst, H. C., et al. (2012) · Molecular Endocrinology · doi:10.1210/me.2012-1056 · Cited by 47 · cited 19× · see citing works
“Given the effects of p23 upon AR activity (Reebye et al., 2012) and stability (and vice-versa) and since prostate cancer is an AR-driven malignancy, we next investigated whether p23 may also be involved in promoting prostate cancer progression.”
BackgroundMethodInfluentialSelf-citationLi, Z., Zhang, W., Wu, M., et al. (2009) · Blood · doi:10.1182/blood-2009-04-218123 · Cited by 43 · cited 2× · see citing works
“…processes as it has been shown to be upregulated in several tumour types, including lung, prostate and breast as well as acute lymphoblastic leukaemia (Elmore et al., 2008; Krebs et al., 2002; Li et al., 2009; Liu et al., 2012; Mollerup et al., 2003; Oxelmark et al., 2006; Reebye et al., 2012).”
BackgroundIschia, J. J., Fred Saad, C., & Gleave, M. E. (2013) · Current Opinion in Urology · doi:10.1097/mou.0b013e32835e9f1a · Cited by 34 · see citing works
Cathepsin D acts as an essential mediator to promote malignancy of benign prostatic epithelium
Pruitt, F. L., He, Y., Franco, O. E., et al. (2012) · The Prostate · doi:10.1002/pros.22589 · Cited by 33 · see citing works
Properties of the co‐chaperone protein p23 erroneously attributed to ALG‐2 (apoptosis‐linked gene 2)
Mollerup, J., Krogh, T. N., Nielsen, P. F., & Berchtold, M. W. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)01310-3 · Cited by 32 · cited 1× · see citing works
“…processes as it has been shown to be upregulated in several tumour types, including lung, prostate and breast as well as acute lymphoblastic leukaemia (Elmore et al., 2008; Krebs et al., 2002; Li et al., 2009; Liu et al., 2012; Mollerup et al., 2003; Oxelmark et al., 2006; Reebye et al., 2012).”
BackgroundEvolutionary epitopes of Hsp90 and p23: implications for their interaction
Zhu, S., & Tytgat, J. (2004) · The FASEB Journal · doi:10.1096/fj.04-1570hyp · Cited by 31 · cited 1× · see citing works
“…binding site (residues 86e108) and an unstructured carboxyl terminal domain (Ali et al., 2006; Martinez-Yamout et al., 2006; Weikl et al., 1999; Zhu and Tytgat, 2004). p23 is the smallest component of the HSP90 chaperone machinery, with a molecular weight of 23,000 Da, and is mainly known for…”
BackgroundLiu, X., Zou, L.-M., Zhu, L., Zhang, H., Du, C.-H., Li, Z., Gao, C., Zhao, X.-X., Bao, S.-L., & Zheng, H.-Y. (2012) · Leukemia research : a Forum for Studies on Leukemia and Normal Hemopoiesis · doi:10.1016/j.leukres.2012.05.003 · Cited by 27 · cited 1× · see citing works
“…processes as it has been shown to be upregulated in several tumour types, including lung, prostate and breast as well as acute lymphoblastic leukaemia (Elmore et al., 2008; Krebs et al., 2002; Li et al., 2009; Liu et al., 2012; Mollerup et al., 2003; Oxelmark et al., 2006; Reebye et al., 2012).”
BackgroundAnalysis of Molecular Chaperone Activities Using In Vitro and In Vivo Approaches
Freeman, B., Michels, A. A., Song, J., Kampinga, H. H., & Morimoto, R. I. (2003) · Humana Press eBooks · doi:10.1385/1-59259-054-3:393 · Cited by 27 · see citing works
Castillo‐Tong, D. C., Heinze, G., Pils, D., et al. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-682 · Cited by 25 · cited 1× · see citing works
“KYNU, CTSD and PMP22 are known to be up-regulated in advanced metastatic cancers and correlate with poor prognosis whereas LAMB1 encodes a laminin-1 protein shown to have reduced expression in breast cancer (Minn et al., 2005; Pruitt et al., 2013; Simpson et al., 2010; Tong et al., 2010).”
BackgroundElmore (1994) · Oncology Reports · doi:10.3892/or_00000049 · Cited by 18 · see citing works
Simpson, N. E., Gertz, J., Imberg-Kazdan, K., Myers, R., & Garabedian, M. J. (2011) · Molecular Endocrinology · doi:10.1210/me.2011-1068 · Cited by 17 · cited 3× · see citing works
“Previously Simpson et al. demonstrated that, in breast cancer cells, p23 modulates the expression of a set of genes dysregulated in advanced breast cancer including those involved in migration, invasion, metabolism or transcriptional regulation (Simpson et al., 2012, 2010).”
BackgroundGlobal Identification of Androgen Response Elements
Massie, C. E., & Mills, I. G. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-243-4_15 · Cited by 16 · cited 2× · see citing works
“It is unlikely that these effects occur at the genomic level given that p23 has not been described to bind any regulatory regions in the vicinity of the AR gene (Massie and Mills, 2011; Sharma et al., 2013) and addition of Mib did not significantly alter p23 gene expression (Supplementary Figure S2).”
BackgroundSimpson, N., Lambert, W. M., Watkins, R. A., Giashuddin, S., Huang, S., Oxelmark, E., Arju, R., Hochman, T., Goldberg, J. D., Schneider, R. J., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1590 · Cited by 11 · see citing works
Flagged first, then by citations
2 of the 52 references couldn’t be matched to a known paper.
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Heat Shock Proteins Promote Cancer: It's a Protection Racket
Calderwood, S. K., & Gong, J. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.01.003 · Cited by 405 · see citing works
“In addition, elevated co-chaperone levels also promote (prostate) cancer; increased levels of the Hsp90 co-chaperone p23 increases metastasis in prostate cancer[70].”
BackgroundAilanthone targets p23 to overcome MDV3100 resistance in castration-resistant prostate cancer
He, Y., Peng, S., Wang, J., Chen, H., Cong, X., Chen, A., Hu, M., Qin, M., Wu, H., Gao, S., et al. (2016) · Nature Communications · doi:10.1038/ncomms13122 · Cited by 105 · see citing works
Kabakov, A. E., Yakimova, A. O., & Николаевна, М. О. (2020) · Cells · doi:10.3390/cells9040892 · Cited by 109 · see citing works
“For instance, the co-chaperone p23 was shown to contribute to the acquisition by prostate cancer cells of a more aggressive (CSC-resembling) phenotype with higher cell motility and pronounced capacity for invasion and metastasis formation [90].”
BackgroundSerwetnyk, M. A., & Blagg, B. S. J. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.11.015 · Cited by 97 · see citing works
Leach, D. A., Mohr, A., Giotis, E. S., Cil, E., Isac, A. M., Yates, L. L., Barclay, W., Zwacka, R. M., Bevan, C. L., & Brooke, G. N. (2021) · Nature Communications · doi:10.1038/s41467-021-24342-y · Cited by 87 · see citing works
Self-citationPappas, B., Yang, Y., Wang, Y., Kim, K., Chung, H. J., Cheung, M., Ngo, K., Shinn, A. H., & Chan, W. K. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.03.015 · Cited by 58 · see citing works
Inhibition of microsomal prostaglandin E synthase-1 as targeted therapy in cancer treatment
Larsson, K., & Jakobsson, P. (2015) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2015.06.002 · Cited by 29 · see citing works
Daneri-Becerra, C., Valeiras, B., Gallo, L. I., Lagadari, M., & Galigniana, M. D. (2020) · Journal of Cell Science · doi:10.1242/jcs.253401 · Cited by 28 · see citing works
Yu, Z., Peng, Y., Gao, J., Zhou, M., Shi, L., Zhao, F. H., Wang, C., Tian, X., Feng, L., Huo, X., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade0387 · Cited by 23 · see citing works
Wang, C., Li, H.-F., Wang, X., Li, W.-G., Su, Q., Xiao, X., Hao, T., Chen, W., Zhang, Y., Zhang, H.-Y., et al. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.60674 · Cited by 20 · see citing works
RNF8 up-regulates AR/ARV7 action to contribute to advanced prostate cancer progression
Zhou, T., Wang, S., Song, X., Liu, W., Dong, F., Huo, Y., Zou, R., Wang, C., Zhang, S., Liu, W., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04787-9 · Cited by 14 · see citing works
Hsp90 Co-chaperones as Drug Targets in Cancer: Current Perspectives
Edkins, A. L. (2016) · Topics in medicinal chemistry · doi:10.1007/7355_2015_99 · Cited by 13 · see citing works
“These effects of gedunin in cells were similar to those observed with depletion of p23 by RNAi [59].”
BackgroundMethodInfluentialTissue proteomics outlines AGR2 AND LOX5 as markers for biochemical recurrence of prostate cancer
Blanco, G. R., Zeneyedpour, L., Duijvesz, D., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.26342 · Cited by 12 · see citing works
“It is involved in AR binding to chromatin, which is a critical step in AR signalling and PCa development [32, 33].”
BackgroundLi, H., Melnyk, J. E., Fu, B. X. H., Shrestha, R., Zhang, M., Sjöström, M., Feng, S., Anderson, J. A., Han, W., Chesner, L. N., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02388-8 · Cited by 10 · see citing works
Comprehensive pan-cancer analysis of PTGES3 and its prognostic role in hepatocellular carcinoma
Wang, H., Sun, P., Yao, R., Zhang, W., Zhou, X., Yao, J., & He, K. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1158490 · Cited by 10 · see citing works
Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer
Backe, S. J., Sager, R., Meluni, K. A., Woodford, M. R., Bourboulia, D., & Mollapour, M. (2022) · Biomolecules · doi:10.3390/biom12070928 · Cited by 9 · see citing works
Targeting the COX/mPGES-1/PGE2 Pathway in Neuroblastoma
Larsson, K., Kock, A., Kogner, P., & Jakobsson, P. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-21735-8_9 · Cited by 10 · see citing works
PTGES3 proteolysis using the liposomal peptide-PROTAC approach
Liu, S., Yuan, F., Dong, H., Zhang, J., Mao, X., Liu, Y., & Li, H. (2024) · Biology Direct · doi:10.1186/s13062-024-00580-0 · Cited by 8 · see citing works
Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity
Backe, S. J., Woodford, M. R., Ahanin, E. F., Sager, R., Bourboulia, D., & Mollapour, M. (2022) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-14740-1_11 · Cited by 8 · see citing works
Bhatti, M., Dinn, S., Miskiewicz, E. I., & MacPhee, D. J. (2019) · Reproductive Biology · doi:10.1016/j.repbio.2019.09.003 · Cited by 8 · see citing works
Androgens’ Role in Severity and Mortality Rates of COVID-19
Ataei, A., Derakhshan, M. M., Razmjooie, M., Zare, F., Amiresmaeili, H., Salehi, N., Namakkoobi, N., Mirhosseini, H., Karim, B., & Iravani, S. (2022) · Hormone and Metabolic Research · doi:10.1055/a-1954-5605 · Cited by 6 · see citing works
“several molecular studies have proved that TmPRss2 is a target gene of AR in prostate cancer cells [28, 43, 44].”
BackgroundSerum HSF1 is upregulated in endometriosis patients and serves as a potential diagnostic biomarker
Pan, H., & Wan, J. (2023) · The Kaohsiung Journal of Medical Sciences · doi:10.1002/kjm2.12723 · Cited by 6 · see citing works
“32,33 HSP90AA1, a member of the HSP90 family, is a potential molecular target for cancer treatment.”
Mellentine, S. Q., Ramsey, A. S., Li, J., Brown, H. N., & Tootle, T. L. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1257751 · Cited by 5 · see citing works
“WhichcellsproducePGE 2 and PGF 2 α to regulate these different downstream effectors remains to be determine. migration (Cano et al., 2015).”
Luo, M., Xu, Q., Sun, Y., He, N., Wen, Z., Wang, Z., Zhao, J., & Liu, Y. (2025) · Shock · doi:10.1097/shk.0000000000002623 · Cited by 5 · see citing works
Combined Thermotherapy and Heat Shock Protein Modulation for Tumor Treatment
Hoter, A., Alsantely, A., Alsharaeh, E. H., Kulik, G., & Saadeldin, I. M. (2020) · Heat shock proteins · doi:10.1007/7515_2020_13 · Cited by 5 · see citing works
Leach, D. A., Mohr, A., Giotis, E. S., Isac, A. M., Yates, L. L., Barclay, W., Zwacka, R. M., Bevan, C. L., & Brooke, G. N. (2021) · doi:10.21203/rs.3.rs-137931/v1 · Cited by 2 · see citing works
Self-citationFRET Assays for the Identification of C. albicans HSP90-Sba1 and Human HSP90α-p23 Binding Inhibitors
Kohlmann, P., Krylov, S. N., Marchand, P., & Jose, J. (2024) · Pharmaceuticals · doi:10.3390/ph17040516 · Cited by 1 · see citing works
“Co-chaperones of HSP90, such as p23, have been shown to play a role in carcinogenesis [13,14].”
BackgroundCyclophilin A is a mitochondrial factor that forms antiapoptotic complexes with p23Preprint
Daneri-Becerra, C., Valeiras, B., Lagadari, M., & Galigniana, M. D. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.21.261982 · Cited by 1 · see citing works
“…of p23 expression (Mollerup et al., 2003; Oxelmark et al., 2006), the prognosis is worse in prostate cancer patients with increased nuclear localization of p23 (Cano et al., 2015), and its overexpression protect cells against the deleterious actions of Hsp90 inhibitors (Forafonov et al., 2008).”
BackgroundBreguez, G. S., Neves, L. X., Silva, K. T. S., de Freitas, L. M. A., Faria, G. D. O., Isoldi, M. C., Castro‐Borges, W., & de Andrade, M. H. G. (2016) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2016.09.017
Mechanistic Study of p23-Mediated Aryl Hydrocarbon Receptor Expression
Pappas, B. (2018) · Scholarly Commons (University of the Pacific)
Huo, M., Zhang, C., Wang, C., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-130892/v1
“P23 is proven to promote breast cancer metastasis and affect its prognosis [42]; it also promotes the invasion and metastasis of prostate cancer[42, 43], and targeting P23 can treat castration-resistant prostate cancer[8].”
BackgroundMellentine, S. Q., Ramsey, A. S., Li, J., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.23.546291
“However, cPGES is also implicated in cancer migration (Cano et al., 2015).”
Cronin, R., Azadova, A., Marco, A. D., Laissue, P. P., Brooke, G. N., & Prischi, F. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.04.582739
Self-citation
- Authors
- Querol Cano, L., Lavery, D. N., Sin, S., Spanjaard, E., Brooke, G. N., Tilman, J. D., Abroaf, A., Gaughan, L., Robson, C. N., Heer, R., Mauri, F., de Rooij, J., Driouch, K., & Bevan, C. L.
- Affiliations
- Imperial College London (GB)
- Institut Curie (FR)
- University Medical Center Utrecht (NL)
- University of Essex (GB)
- Newcastle University (GB)
- Hammersmith Hospital (GB)
- Corresponding author
- Bevan, Charlotte L.
- ORCID
- Venue
- Molecular Oncology
- Publisher
- Wiley
- Published
- 2014-09-06
- Volume
- 9
- Issue
- 1
- Pages
- 295-308
- ISSN
- 1574-7891 (ISSN-L)
- 1878-0261
- PMC
- PMC4510206
- OpenAlex
- W2158616992
- Semantic Scholar
- feaf80be2ecae4dbbea6f39b2c345835d3f03a80
- Cited by
- 33
- References
- 52
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 3 · 2016: 4 · 2015: 1 · 2014: 1
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Oncology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Access at Essex (University of Essex) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Cancer Research UK (C11509/A9262, C11509/A12426)
- European Association for Cancer Research
- Netherlands Center for Systems Biology
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- p23, prostate cancer, androgen receptor, molecular chaperones, metastasis, cell motility, castration resistance, HSP90 inhibition, 17-AAG, androgen receptor antagonists, androgen receptor signaling, tumour invasiveness, prognosis, combination therapy
- MeSH terms
- Prostaglandin-E Synthases, Cell Movement, Humans, Male, Neoplasm Metastasis, Prostatic Neoplasms, Benzoquinones, HSP90 Heat-Shock Proteins, Intramolecular Oxidoreductases, Cell Line, Tumor, Lactams, Macrocyclic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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