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Cited by 156Protein Degradation and InhibitorsWnt/β-catenin signaling in development and cancerChemical Synthesis and Analysis

A PROTAC peptide induces durable β-catenin degradation and suppresses Wnt-dependent intestinal cancer

Open access
Liao, Hongwei, Li, Xiang, Zhao, Lianzheng, Wang, Yalong, Wang, Xiaodan, Wu, Ye, Zhou, Xin, Fu, Wei +3 more·2020·Cell Discovery
DOI 10.1038/s41421-020-0171-1PMC PMC7280531
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Abstract

Aberrant activation of Wnt/β-catenin signaling has been associated with the onset and progression of many types of tumors and thus β-catenin represents one attractive intracellular target for cancer therapy. Based on the Axin-derived peptide that binds to β-catenin, two stapled peptides SAHPA1 and xStAx were reported to enhance or impair Wnt/β-catenin signaling, respectively. In this study, we designed PROTACs (proteolysis targeting chimeras) by coupling SAHPA1 or xStAx with the VHL ligand to achieve efficient β-catenin degradation. The obtained xStAx-VHLL sustained β-catenin degradation and manifested strong inhibition of Wnt signaling in cancer cells and in APC−/− organoids. Furthermore, xStAx-VHLL could effectively restrain tumor formation in BALB/C nude mice, and diminish the existing tumors in APCmin/+ mice. More importantly, xStAx-VHLL could potently inhibit the survival of colorectal cancer patient-derived organoids. These findings suggest that xStAx-VHLL exhibits the ability of cancer prevention and cure, highlighting the potential of β-catenin degrader PROTACs as a new class of promising anticancer agent.

AI snapshot

Written from the paper’s full text.

TL;DR

The study designed peptide-based PROTACs by coupling the β-catenin-binding stapled peptides SAHPA1 or xStAx to a VHL ligand, yielding xStAx-VHLL as a potent β-catenin degrader. xStAx-VHLL sustained β-catenin degradation, inhibited Wnt signaling, and suppressed tumor growth in cell, organoid, xenograft, APCmin/+, and patient-derived colorectal cancer organoid models.

Key findings

  • xStAx-VHLL induced dose-dependent β-catenin degradation in HEK293T and CRC cells, promoted β-catenin ubiquitination, and its effect was blocked by the proteasome inhibitor MG132 and the VHL inhibitor VH-298.
  • β-catenin remained low after 24 h of xStAx-VHLL washout, whereas β-catenin recovered after xStAx or MSAB removal; xStAx-VHLL also maintained low β-catenin up to 36 h, unlike xStAx.
  • In BALB/C nude mice injected with 3 × 10^6 LoVo cells pretreated with 50 μM peptide, xStAx-VHLL-derived tumors were significantly smaller in size and weight, with decreased β-catenin and reduced Wnt target genes Axin2, Cyclin D1, and Myc.
  • In 11-week-old APCmin/+ mice treated intraperitoneally with 30 mg/kg every other day for 14 days, xStAx-VHLL dramatically reduced intestinal tumor number; xStAx-VHLL also inhibited survival of 11/12 CRC patient-derived organoids at 10 μM over 4 days.

Methods

  • The authors synthesized SAHPA1-VHLL and xStAx-VHLL by conjugating SAHPA1 or xStAx to the VHL ligand ALAPYIP via a 6-aminocaproic acid linker, purified by HPLC, and verified by ESI-MS.
  • Cell models included HEK293T and CRC lines HCT116, SW480, and LoVo; organoid models included wild-type, APC−/−, and 12 patient-derived CRC organoids; mouse models included BALB/C nude xenografts, APCmin/+ mice, and Axin2LacZ reporter mice.
  • Main assays included immunoblotting, immunoprecipitation for β-catenin ubiquitination, Topflash luciferase reporter assays, qRT-PCR for Wnt target genes, cell proliferation counting, organoid survival/budding assays, tumor weight/number measurements, and β-galactosidase staining; statistics used one-way or two-way ANOVA with mean ± SD.

Limitations

  • The paper states that C-11 patient-derived organoids were insensitive to xStAx-VHLL even though β-catenin decreased, possibly because other signaling pathways drive their growth and survival.
  • The paper states that xStAx-VHLL is a first-generation PROTAC and requires further optimization, including non-natural residues in the VHL ligand, double-stapling, alternative E3 ligands, improved β-catenin-binding peptides such as NLS-StAx-h, and more polar PEG linkers of varying length.
  • The paper notes that SAHPA1-VHLL had minimal effect on β-catenin stability and Wnt signaling, possibly due to SAHPA1’s promoting effect and lower membrane permeability compared with xStAx-VHLL; no clinical testing or pharmacokinetic data are reported in the text.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41421-020-0171-1

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

8 of 19 cited sources checked · 5 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    xStAx inhibits Wnt/β-catenin signaling.

    “SAHPA1 was shown to activate Wnt/β-catenin signaling, while xStAx inhibited it13,14.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [13] Cui, H. K. et al. Design of stapled alpha-helical peptides to specifically activate Wnt/beta-catenin signaling. Cell Res. 23, 581–584 (2013). source
    • cites [14] Grossmann, T. N. et al. Inhibition of oncogenic Wnt signaling through direct targeting of beta-catenin. Proc. Natl Acad. Sci. USA 109, 17942–17947 (2012). source
  • Premisecitation

    Wnt/β-catenin signaling is essential to maintain intestinal organoid growth.

    “Wnt/β-catenin signaling is essential to maintain intestinal organoid growth26,27”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [26] Tuveson, D. & Clevers, H. Cancer modeling meets human organoid technology. Science 364, 952–955 (2019). source
    • cites [27] Liu, Y. & Chen, Y. G. 2D-based and 3D-based intestinal stem cell cultures for personalized medicine. Cells 7, E225 (2018). source
  • Premisecitation

    The PROTAC technique can aid small molecule inhibitors or peptides to exert better biological activities in vivo by linking the ubiquitin-proteasome system to induce degradation of targeted proteins.

    “The PROTAC technique could aid small molecule inhibitors or peptides to exert better biological activities in vivo as PROTAC can link the ubiquitin-proteasome system to induce effective degradation of targeted proteins16.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [16] Lai, A. C. & Crews, C. M. Induced protein degradation: an emerging drug discovery paradigm. Nat. Rev. Drug Discov. 16, 101–114 (2017). source

      The Small-molecule PROTACs section (§4; page not provided) explains that PROTACs recruit an E3 ligase to degrade a target and reports mouse-xenograft evidence of better in vivo efficacy than parent inhibitors. The Peptide-based PROTACs section (§4; page not provided) describes peptide-based degradation mainly in cells and notes poor cell penetration; it does not establish better in vivo activity for peptide-based PROTACs. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Findingown data

    Wnt3a induces Topflash-luciferase reporter expression in HEK293T cells.

    “Wnt3a induced the expression of the reporter”
    Quote in the paperSubstantial claim
  • Findingown data

    xStAx-VHLL inhibits Wnt signaling.

    “xStAx-VHLL also efficiently inhibited Wnt signaling as well as cell proliferation, intestinal organoid growth, and tumor formation.”
    Quote in the paperSubstantial claim
  • May combine two claims. 27
  • Classified as probably not a substantial claim. 6
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    SAHPA1 and xStAx are capable of penetrating the cell membrane and binding with β-catenin.

    “Both SAHPA1 and xStAx are capable of penetrating the cell membrane and binding with β-catenin.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [13] Cui, H. K. et al. Design of stapled alpha-helical peptides to specifically activate Wnt/beta-catenin signaling. Cell Res. 23, 581–584 (2013). source

      In the Dear Editor section (page not available), the paper reports that SAHPA1 binds β-catenin and that FITC-labeled SAHPA1 enters the cytoplasm of HeLa cells. It does not identify a peptide called xStAx or establish both properties for it; it discusses a different peptide, fStAx-35R. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [14] Grossmann, T. N. et al. Inhibition of oncogenic Wnt signaling through direct targeting of beta-catenin. Proc. Natl Acad. Sci. USA 109, 17942–17947 (2012). source

      The Results (Fig. 3) report cellular uptake of StAx peptides and their binding to β-catenin, supporting that part of the claim. The paper does not identify a peptide called xStAx or address SAHPA1, so it does not establish the claim for both named peptides. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    SAHPA1 activates Wnt/β-catenin signaling.

    “SAHPA1 was shown to activate Wnt/β-catenin signaling, while xStAx inhibited it13,14.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [13] Cui, H. K. et al. Design of stapled alpha-helical peptides to specifically activate Wnt/beta-catenin signaling. Cell Res. 23, 581–584 (2013). source
    • cites [14] Grossmann, T. N. et al. Inhibition of oncogenic Wnt signaling through direct targeting of beta-catenin. Proc. Natl Acad. Sci. USA 109, 17942–17947 (2012). source

  • May combine two claims.

    Findingown data

    Proliferation of LoVo cells is hampered by xStAx-VHLL but not by MSAB.

    “the proliferation of LoVo cells was hampered by xStAx-VHLL but not by MSAB”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SAHPA1 slightly enhances Wnt3a-induced reporter expression while xStAx inhibits it.

    “SAHPA1 slightly enhanced the Wnt3a effect while xStAx exhibited an inhibitory effect”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    xStAx-VHLL acts as a potent PROTAC β-catenin degrader, promoting proteasomal degradation of endogenous β-catenin in cancer cells and intestinal organoids.

    “We demonstrated that xStAx-VHLL acted as a potent PROTAC β-catenin degrader, efficiently promoting the proteasomal degradation of endogenous β-catenin in cancer cells and intestinal organoids.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    xStAx-VHLL treatment reduces β-catenin protein level and increases cleaved caspase 3 level in wild-type organoids.

    “xStAx-VHLL treatment reduced the β-catenin protein level while increased the cleaved caspase 3 level”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    xStAx-VHLL induces durable degradation of β-catenin in HEK293T cells as long as 24 h post washout, while β-catenin protein level is restored after 24 h of MSAB removal.

    “xStAx-VHLL induced the durable degradation of β-catenin in HEK293T cells as long as 24 h post washout, while β-catenin protein level was restored after 24 h of MSAB removal”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    C-11 organoids are insensitive to xStAx-VHLL even though β-catenin protein level is decreased.

    “C-11 organoids, which harbored the mutations of LRP6, APC, TCF7L2, KRAS, TP53, and others, were insensitive to xStAx-VHLL, even though the β-catenin protein level was decreased”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    β-catenin protein level is greatly decreased after 24 h treatment of xStAx-VHLL in APC−/− organoids, whereas cleaved caspase 3 increases.

    “β-catenin protein level in of the organoids was greatly decreased after 24 h treatment of xStAx-VHLL, whereas the cleaved caspase 3 increased”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Lgr5+ intestinal stem cells are reduced after 36 h treatment of xStAx-VHLL, and the viable cell population decreases.

    “Lgr5+ intestinal stem cells were reduced after 36 h treatment of xStAx-VHLL, and the viable cell population also decreased”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    xStAx-VHLL sustains β-catenin degradation in cancer cells and APC−/− organoids.

    “The obtained xStAx-VHLL sustained β-catenin degradation and manifested strong inhibition of Wnt signaling in cancer cells and in APC−/− organoids.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In LoVo cells, only xStAx-VHLL reduces β-catenin protein level, while MSAB has no effect.

    “in LoVo cells, only xStAx-VHLL was able to reduce the β-catenin protein level, while MSAB had no effect”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The inhibitory effect of xStAx-VHLL is observed in systems with intact Wnt/β-catenin signaling and in systems with APC-defective and constitutively active β-catenin mutations.

    “This inhibitory effect was observed not only in the systems with intact Wnt/β-catenin signaling, but also in the systems with APC-defective and constitutively active β-catenin mutations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Tumors from xStAx-VHLL-pretreated LoVo cells are significantly smaller in size and weight in BALB/C nude mice.

    “the tumors originated from xStAx-VHLL pretreating cells were significantly smaller in size and weight”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    xStAx-VHLL effectively restrains survival of CRC patient-derived tumor organoids, potently inhibiting 11/12 tested patient-derived tumor organoids.

    “Further, in CRC patient-derived tumor organoids, xStAx-VHLL effectively restrained the survival of tumor organoids, which highlighted its clinical potential.”
    • Also stated in: § Discussion · boosted
      “In this study, we have found that a potent inhibition of 11/12 patient-derived tumor organoids by xStAx-VHLL not only reveals that xStAx-VHLL is a promising anti-CRC drug candidate, but also confirms that the patient-derived tumor organoids exhibit their advances in testing the effectiveness of PROTAC peptides.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SAHPA1 slightly enhances β-catenin level while xStAx decreases it in HEK293T cells.

    “SAHPA1 slightly enhanced the β-catenin level while xStAx decreased it.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    xStAx-VHLL achieves strong inhibition on APC−/− organoid survival, whereas MSAB has a minimal effect.

    “xStAx-VHLL achieved a strong inhibition on APC−/− organoid survival, whereas MSAB had a minimal effect”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both xStAx and xStAx-VHLL start to induce β-catenin degradation as soon as 12 h post treatment.

    “Both xStAx and xStAx-VHLL started to induce β-catenin degradation as soon as 12 h post treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    xStAx and xStAx-VHLL have similar membrane permeability and efficiently enter cells.

    “both xStAx and xStAx-VHLL had similar membrane permeability and could efficiently enter into a cell”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Trypan blue staining at day 4 indicated dead C-08 organoids after xStAx-VHLL treatment.

    “The trypan blue staining at day 4 indicated the dead organoids.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    SAHPA1-VHLL has minimal effect on β-catenin stability and little effect on Wnt/β-catenin signaling, unlike xStAx-VHLL.

    “Although both SAHPA1 and xStAx were derived the same β-catenin-binding peptide, unlike xStAx-VHLL, SAHPA1-VHLL had minimal effect on β-catenin stability and thus no much effect on Wnt/β-catenin signaling.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    xStAx-VHLL is more potent than xStAx in inhibiting Wnt/β-catenin signaling and attenuating cell proliferation and organoid growth.

    “Indeed, xStAx-VHLL was more potent than xStAx to inhibit Wnt/β-catenin signaling and attenuate cell proliferation and organoid growth.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    APCmin/+ mice harbor a point mutation in the APC gene, resulting in APC deletion and constitutive activation of Wnt signaling.

    “APCmin/+ mice that harbored a point mutation in the APC gene, resulting in APC deletion and constitutive activation of Wnt signaling25”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Fearon, E. R. & Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 61, 759–767 (1990). source

  • May combine two claims.

    Interpretationown data

    xStAx-VHLL impedes CRC cell proliferation and restrains tumor formation.

    “These data suggest that xStAx-VHLL impedes CRC cells proliferation and restrains tumor formation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    xStAx-VHLL exhibits the ability of cancer prevention and cure.

    “These findings suggest that xStAx-VHLL exhibits the ability of cancer prevention and cure”
    Quote in the paperSubstantial claim
    • Rests on an assumption: In the majority of CRC patients, Wnt/β-catenin signaling is aberrantly activated.
    • Rests on an assumption: The 12 CRC patient-derived organoids are representative of CRC patient tumors and their responses to xStAx-VHLL predict clinical response.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Synthesized PROTACs were obtained with over 95% purities, as verified by ESI-MS.

    “the synthesized PROTACs were readily obtained with over 95% purities, as verified by ESI-MS”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Targeting β-catenin is regarded as an important approach to treat cancers with activated Wnt/β-catenin signaling.

    “As Wnt/β-catenin signaling pathway is activated in various cancers, including colorectal cancer, targeting β-catenin has been regarded as an important approach to treat these diseases4,5.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4] Nusse, R. & Clevers, H. Wnt/beta-catenin signaling, disease, and emerging therapeutic modalities. Cell 169, 985–999 (2017). source
    • cites [5] Cui, C., Zhou, X., Zhang, W., Qu, Y. & Ke, X. Is beta-catenin a druggable target for cancer therapy? Trends Biochem. Sci. 43, 623–634 (2018). source

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationown data

    xStAx-VHLL has shown great promise in inhibiting tumor growth in vivo and could be employed as the leading PROTAC for further optimization in Wnt signaling-interfering cancer therapy.

    “Nonetheless, as the first-generation PROTAC β-catenin degrader, xStAx-VHLL has already showed great promise in inhibiting tumor growth in vivo, and it could be employed as the leading PROTAC for further optimization in Wnt signaling-interfering cancer therapy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Patient-derived tumor organoids recapitulate tumor complexity and heterogeneity and are an ideal model for drug screening and precision medicine.

    “The patient-derived tumor organoids, which recapitulate the complexity and heterogeneity of tumors, have been shown to be an ideal model for drug screening and precision medicine26.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Tuveson, D. & Clevers, H. Cancer modeling meets human organoid technology. Science 364, 952–955 (2019). source

  • May combine two claims.

    Premisecitation

    xStAx inhibits Wnt/β-catenin signaling but may be less efficient for in vivo tumor treatment because newly synthesized β-catenin can rapidly accumulate.

    “Although xStAx designed by Grossmann and coworkers exhibited an impressive inhibition on Wnt/β-catenin signaling, it could be less efficient for in vivo use to treat tumors as the newly synthesized β-catenin can rapidly accumulate30.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Li, V. S. et al. Wnt signaling through inhibition of beta-catenin degradation in an intact Axin1 complex. Cell 149, 1245–1256 (2012). source

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All experiments were carried out with at least three biological replicates.

    “All experiments were carried out with at least three biological replicates.”
    • Also stated in: § xStAx-VHLL restrains the survival of CRC patient-derived organoids · plain
      “Data from three independent experiments are displayed as the mean ± SD by two-way ANOVA (a, c) and one-way ANOVA (d, g).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (M2018083) and all relevant ethical regulations were followed.

    “All samples were obtained with informed consent, and the study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (M2018083). All relevant ethical regulations of Peking University Third Hospital Medical Science Research Ethics Committee were followed.”
    Quote in the paperNot a substantial claim
32 of 32

  • The paper relies on this without support.

    In the majority of CRC patients, Wnt/β-catenin signaling is aberrantly activated.

    “In the majority of CRC patients, Wnt/β-catenin signaling is aberrantly activated.”

  • The paper relies on this without support.

    The 12 CRC patient-derived organoids are representative of CRC patient tumors and their responses to xStAx-VHLL predict clinical response.

    “we were able to test the clinical potential of β-catenin targeted degrader xStAx-VHLL ex vivo”

  • The paper relies on this without support.

    The specificity of small molecules is a general concern.

    “However, the specificity of small molecules is a general concern.”

  • The paper relies on this without support.

    Traditional drug discovery relies on cell-based or animal models, and few candidate drugs succeed in patient-based clinical studies.

    “Traditional drug discovery heavily relies on cell-based or animal models, few of the candidate drugs succeed in patient-based clinical studies.”
4 of 4

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?

  • xStAx-VHL is a peptide-based PROTAC that degrades β-catenin via the ubiquitin-proteasome pathway, inhibiting Wnt signaling at the cellular level and demonstrating oncogenic effects in various mouse tumor models and colon cancer patients.

    “In 2020, Chen’s team reported the use of peptide-based PROTACs for TPD, introducing xStAx-VHL, a peptide-based PROTAC, to degrade β-catenin. This PROTAC directly recognizes the protein and promotes its degradation via the ubiquitin-proteasome pathway, inhibiting Wnt signaling at the cellular level and demonstrating oncogenic effects in various mouse tumor models and colon cancer patients.532”

    From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [532]

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.

  • Fig. 6e identifies the wrong patient-derived organoids

    Minor

    The results text identifies Fig. 6e-g as showing the insensitive C-11 organoids, whereas the Fig. 6e caption identifies its organoids as C-08.

  • Fig. 2 comparison was not conducted at 10 μM for all other inhibitors

    Minor

    The results describe the other inhibitors as being used at 10 μM, but the Fig. 2c caption specifies 20 μM PRI-724 and 100 μM PNU-74654.

  • HEK293T xStAx-VHLL concentration differs between text and Fig. 2d caption

    Minor

    The results state that HEK293T cells received 50 μM xStAx-VHLL for the comparison with MSAB, while the Fig. 2d caption specifies 70 μM.

  • Different concentrations reported for the APC−/− organoid survival experiment

    Minor

    The Fig. 5 caption says APC−/− organoids were treated with 50 μM peptides, but its description of the survival measurements for the same experiment says 10 μM.

4 of 4

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Authors
Liao, H., Li, X., Zhao, L., Wang, Y., Wang, X., Wu, Y., Zhou, X., Fu, W., Liu, L., Hu, H.-G., & Chen, Y.-G.
Affiliations
  • Center for Life Sciences (CN)
  • Second Military Medical University (CN)
  • Peking University Third Hospital (CN)
Corresponding author
Chen, Ye-Guang
ORCID
Venue
Cell Discovery
Publisher
Springer Science and Business Media LLC
Published
2020-06-09
Volume
6
Issue
1
Pages
35-35
ISSN
2056-5968 (ISSN-L)
DOI
10.1038/s41421-020-0171-1
PMC
PMC7280531
OpenAlex
W3034021518
Cited by
156
References
37
Citations by year
2026: 18 · 2025: 30 · 2024: 40 · 2023: 31 · 2022: 19 · 2021: 10 · 2020: 4
FWCI
4.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Discovery (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
Keywords
PROTACs, β-catenin degradation, Wnt/β-catenin signaling, stapled peptides, colorectal cancer, ApcMin/+ mice, patient-derived organoids, targeted protein degradation

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