The DOI matches its Crossref record; 59 of the 61 references it cites were found in a registry or an index.
Mutant p53 Drives Pancreatic Cancer Metastasis through Cell-Autonomous PDGF Receptor β Signaling
Open accessAbstract
Missense mutations in the p53 tumor suppressor inactivate its antiproliferative properties but can also promote metastasis through a gain-of-function activity. We show that sustained expression of mutant p53 is required to maintain the prometastatic phenotype of a murine model of pancreatic cancer, a highly metastatic disease that frequently displays p53 mutations. Transcriptional profiling and functional screening identified the platelet-derived growth factor receptor b (PDGFRb) as both necessary and sufficient to mediate these effects. Mutant p53 induced PDGFRb through a cell-autonomous mechanism involving inhibition of a p73/NF-Y complex that represses PDGFRb expression in p53-deficient, noninvasive cells. Blocking PDGFRb signaling by RNA interference or by small molecule inhibitors prevented pancreatic cancer cell invasion in vitro and metastasis formation in vivo. Finally, high PDGFRb expression correlates with poor disease-free survival in pancreatic, colon, and ovarian cancer patients, implicating PDGFRb as a prognostic marker and possible target for attenuating metastasis in p53 mutant tumors.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“altered p53 function has a multitude of tumor-promoting effects on neoplastic cells, including increased genomic instability30, reprogrammed cellular metabolism57,58, and enhanced metastatic propensity59.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [59]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
Self-citationDifferential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
Spencer, P. M., Cameron, J. L., & Lin, L. (2000) · Cited by 7,202
Landscape of transcription in human cells
Djebali, S., Davis, C. A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F., et al. (2012) · Nature · doi:10.1038/nature11233 · Cited by 5,187
Self-citationCore Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969 · cited 1×
“Notably, the c-KIT and BCR-ABL kinases have not been linked to PDAC development (Jones et al., 2008).”
Hingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609
Hidalgo, M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0901557 · Cited by 2,570
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00309-x · Cited by 2,471
TRANSFAC(R) and its module TRANSCompel(R): transcriptional gene regulation in eukaryotes
Matys, V. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj143 · Cited by 2,142 · cited 1×
“To better understand how p73 represses PDGFRB transcription, we performed chromatin immunoprecipitation (ChIP) analysis in KPflC cells but failed to detect direct binding of p73 to the PDGFRB promoter (data not shown), a result consistent with previous reports (Matys et al., 2006).”
Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes
Initiative, A. P. C. G., Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., et al. (2012) · Nature · doi:10.1038/nature11547 · Cited by 2,058
Self-citation
Cited by
Sorted by citations
Genomic analyses identify molecular subtypes of pancreatic cancer
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., et al. (2016) · Nature · doi:10.1038/nature16965 · Cited by 3,621
Self-citationKastenhuber, E. R., & Lowe, S. W. (2017) · Cell · doi:10.1016/j.cell.2017.08.028 · Cited by 1,906
Self-citationPancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321
Perturbation-response genes reveal signaling footprints in cancer gene expression
(2017) · doi:10.1038/s41467-017-02391-6 · Cited by 1,108
“…mutations and loss are in line with the recent discovery that TP53 mutations can act in an oncogenic manner in addition to disrupting its tumor suppressor activity, which has been shown for individual cancer types (Olive et al. 2004; Zhang et al. 2013; Weissmueller et al. 2014; Zhu et al. 2015).”
BackgroundKrebs, A. M., Mitschke, J., Losada, M. L., Schmalhofer, O., Boerries, M., Busch, H. S., Böttcher, M., Mougiakakos, D., Reichardt, W., Bronsert, P., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3513 · Cited by 1,008
Self-citationMolecular subtypes of pancreatic cancer
Collisson, E. A., Bailey, P., Chang, D. K., & Biankin, A. V. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0109-y · Cited by 892
Self-citationFibroblast heterogeneity in the cancer wound
Öhlund, D., Elyada, E., & Tuveson, D. A. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20140692 · Cited by 982
Evolving therapeutic landscape of advanced hepatocellular carcinoma
Yang, C. G., Zhang, H., Zhang, L., Zhu, A. X., Bernards, R., Qin, W., & Wang, C. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00704-9 · Cited by 747
Cancer-associated fibroblasts in gastrointestinal cancer
Kobayashi, H., Enomoto, A., Woods, S. L., Burt, A. D., Takahashi, M., & Worthley, D. L. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0115-0 · Cited by 609
Tumor microenvironment participates in metastasis of pancreatic cancer
Ren, B., Cui, M., Yang, G., Wang, H., Feng, M., You, L., & Zhao, Y. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0858-1 · Cited by 597
“the expression of PDGF receptor β correlates with poor disease-free survival in pancreatic cancer patients [152, 153].”
BackgroundTargeting mutant p53 for cancer therapy: direct and indirect strategies
Hu, J., Cao, J., Topatana, W., Juengpanich, S., Li, S., Zhang, B., Shen, J., Cai, L., Cai, X., & Chen, M. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01169-0 · Cited by 576
Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others
Sabapathy, K., & Lane, D. P. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.151 · Cited by 517
Understanding the complexity of p53 in a new era of tumor suppression
Liu, Y., Su, Z., Tavana, O., & Gu, W. J. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.04.009 · Cited by 538
Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth
Zhu, J., Sammons, M. A., Donahue, G., Dou, Z., Vedadi, M., Getlik, M., Barsyte-Lovejoy, D., Al-awar, R., Katona, B. W., Shilatifard, A., et al. (2015) · Nature · doi:10.1038/nature15251 · Cited by 493
Enhancer Reprogramming Promotes Pancreatic Cancer Metastasis
Roe, J., Hwang, C., Somerville, T. D. D., Milazzo, J. P., Lee, E. J., Silva, B. D., Maiorino, L., Tiriac, H., Young, C. M., Miyabayashi, K., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.007 · Cited by 465
“…changes to those observed in a prior microarray evaluation of human PDA samples (Moffitt et al., 2015), including upregulation of known regulators of PDA metastasis, Lin28b, Pdgfrb, and Runx3 (Figures S2A and S2B) (Kugel et al., 2016; Weissmueller et al., 2014; Whittle et al., 2015).”
Mutant p53 as a target for cancer treatment
Duffy, M. J., Synnott, N. C., & Crown, J. P. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2017.06.023 · Cited by 369
Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment
Alexandrova, E. M., Yallowitz, A. R., Li, D., Xu, S., Schulz‐Heddergott, R., Proia, D. A., Lozano, G., Dobbelstein, M., & Moll, U. M. (2015) · Nature · doi:10.1038/nature14430 · Cited by 359
Mutant p53 Suppresses Innate Immune Signaling to Promote Tumorigenesis
Ghosh, M., Saha, S., Bettke, J. A., Nagar, R., Parrales, A., Iwakuma, T., van der Velden, A. W. M., & Martinez, L. A. (2020) · Cancer Cell · doi:10.1016/j.ccell.2021.01.003 · Cited by 355
Gain-of-function mutant p53 in cancer progression and therapy
Zhang, C., Liu, J., Xu, D., Zhang, T., Hu, W., & Feng, Z. (2020) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjaa040 · Cited by 358
“Mutp53 sequesters p73 from forming the complex with NF-Y, activating PDGF receptor b (PDGFRb) signaling to promote pancreatic cancer metastasis (Weissmueller et al., 2014).”
BackgroundCell death in pancreatic cancer: from pathogenesis to therapy
Chen, X., Zeh, H. J., Kang, R., Kroemer, G., & Tang, D. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00486-6 · Cited by 344
Vallabhaneni, K. C., Penfornis, P., Dhule, S. S., Guillonneau, F., Adams, K. V., Mo, Y. Y., Xu, R., Liu, Y., Watabe, K., Vemuri, M. C., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.3211 · Cited by 334
“As a proof of concept we have confirmed expression of 7 proteins; two proteins confirm the origin of the hMSCs EVs (CD90 and CD81) [37] and five known proteins associated with tumor proliferation and anti-metastasis [38-42].”
BackgroundMacrophage PI3Kγ Drives Pancreatic Ductal Adenocarcinoma Progression
Kaneda, M. M., Cappello, P., Nguyen, A. V., Ralainirina, N., Hardamon, C. R., Foubert, P., Schmid, M. C., Sun, P., Mose, E. S., Bouvet, M., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1346 · Cited by 338
The enhancement of glycolysis regulates pancreatic cancer metastasis
Yang, J., Ren, B., Yang, G., Wang, H., Chen, G., You, L., Zhang, T., & Zhao, Y. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03278-z · Cited by 347
Kim, M. P., & Lozano, G. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.185 · Cited by 313
“In pancreatic cancer KPC cells, mutant p53R175H and R273H may bind to p73 and prevent its binding to NF-Y on the PDGFRβ promoter, allowing PDGFRβ expression.(18) The TF NF-Y binds the p53 missense mutants R175H and 273C, transactivating pro-cell cycle genes.”
Backgroundα-Ketoglutarate links p53 to cell fate during tumour suppression
Morris, J. P., Yashinskie, J. J., Koche, R., Chandwani, R., Tian, S., Chen, C.-C., Baslan, T., Marinkovic, Z. S., Sánchez-Rivera, F. J., Leach, S. D., et al. (2019) · Nature · doi:10.1038/s41586-019-1577-5 · Cited by 296
Self-citationMiller, B. W., Morton, J. P., Pinese, M., Saturno, G., Jamieson, N. B., McGhee, E. J., Timpson, P., Leach, J. D. G., McGarry, L., Shanks, E. J., et al. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201404827 · Cited by 299
“From this, a single signature was identified (called PC-1) that following crossvalidation could predict survival in the discovery cohort (Fig 1A).”
Self-citationSignaling pathways in cancer‐associated fibroblasts: recent advances and future perspectives
Fang, Z., Meng, Q., Xu, J., Wang, W., Zhang, B., Liu, J., Liang, C., Hua, J., Zhao, Y., Yu, X., et al. (2022) · 癌症：英文版 · doi:10.1002/cac2.12392 · Cited by 304
Nakayama, M., & Oshima, M. (2018) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjy075 · Cited by 294
Vennin, C., Mélénec, P., Rouet, R., Nobis, M., Cazet, A. S., Murphy, K. J., Herrmann, D., Reed, D. A., Lucas, M. C., Warren, S. C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10968-6 · Cited by 268
Self-citationThe kinome 'at large' in cancer
Fleuren, E. D. G., Zhang, L., Wu, J., & Daly, R. J. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2015.18 · Cited by 268
Self-citationPrincipe, D. R., Underwood, P. W., Korc, M., Trevino, J. G., Munshi, H. G., & Rana, A. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.688377 · Cited by 273
Walerych, D., Lisek, K., Sommaggio, R., Piazza, S., Ciani, Y., Dalla, E., Rajkowska, K., Gaweda-Walerych, K., Ingallina, E., Tonelli, C., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3380 · Cited by 239
Helms, E. J., Berry, M. W., Chaw, R. C., DuFort, C. C., Sun, D., Onate, M. K., Oon, C., Bhattacharyya, S., Sanford-Crane, H., Horton, W., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0601 · Cited by 238
Molecular Pathogenesis of Pancreatic Cancer
Grant, T. J., Hua, K., & Singh, A. (2016) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2016.09.008 · Cited by 237
Sun, X., He, X., Zhang, Y., Hosaka, K., Andersson, P., Wu, J., Wu, J., Xu, J., Du, Q., Hui, X., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-322744 · Cited by 240
Self-citationLiu, J., Li, P., Wang, L., Li, M., Ge, Z., Noordam, L., Lieshout, R., Verstegen, M. M. A., Ma, B., Su, J., et al. (2020) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2020.09.003 · Cited by 211
Therapeutic targeting of tumor suppressor genes
Morris, L. G. T., & Chan, T. A.-T. (2014) · Cancer · doi:10.1002/cncr.29140 · Cited by 209
“able to significantly reduce the invasive potential of models of pancreatic adenocarcinoma.(40)”
BackgroundMutant p53: it’s not all one and the same
Kennedy, M. C., & Lowe, S. W. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-00989-y · Cited by 211
“For example, the best characterized GOF activity of mutant p53 is its role in promoting metastasis [43, 48].”
BackgroundSelf-citationRole and regulation of autophagy in cancer
Rakesh, R., Dharshini, L. C. P., Sakthivel, K. M., & Rasmi, R. R. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2022.166400 · Cited by 198
p53 mutations cooperate with oncogenic Kras to promote adenocarcinoma from pancreatic ductal cells
Bailey, J. M., Hendley, A. M., Lafaro, K. J., Pruski, M. A., Jones, N. C., Alsina, J., Younes, M., Maitra, A., McAllister, F., Iacobuzio-Donahue, C. A., et al. (2016) · Oncogene · doi:10.1038/onc.2015.441 · Cited by 154
Altered RNA Splicing by Mutant p53 Activates Oncogenic RAS Signaling in Pancreatic Cancer
Escobar‐Hoyos, L. F., Penson, A., Kannan, R., Cho, H., Pan, C., Singh, R. K., Apken, L. H., Hobbs, G. A., Luo, R., Lecomte, N., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.05.010 · Cited by 161
“Inducible shRNAs against TP53 and Trp53 (human andmurine p53) or renilla (R) were cloned into the TRMPV-Neo vector (pSIN-TREdsRed-miR30-PGK-Venus-IRES-NeoR) as previously described (Weissmueller et al., 2014; Zuber et al., 2011).”
BackgroundMethodSelf-citationGain-of-Function Mutant p53: All the Roads Lead to Tumorigenesis
Stein, Y., Rotter, V., & Aloni-Grinstein, R. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20246197 · Cited by 169
Kim, M. P., Li, X., Deng, J., Zhang, Y., Dai, B., Allton, K. L., Hughes, T. G., Siangco, C., Augustine, J. J., Kang, Y., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1228 · Cited by 164
“Other work has indicated that mutant p53 mediates PDAC metastasis through upregulation of the receptor tyrosine kinase (RTK), platelet derived growth factor receptor-β (PDGFR-β) (11).”
BackgroundMutant p53 on the Path to Metastasis
Tang, Q., Su, Z., Gu, W., & Rustgi, A. K. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.11.004 · Cited by 155
Osteosarcoma: Molecular Pathogenesis and iPSC Modeling
Lin, Y.-H., Jewell, B. E., Gingold, J., Lu, L., Zhao, R., Wang, L. L., & Lee, D.-F. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.06.004 · Cited by 150
“Mutant p53 also upregulates PDGFRb by inhibiting the p73/NF-Y complex, leading to further invasion and metastasis in a pancreatic cancer mouse model [37].”
BackgroundThe p53 family and the hypoxia-inducible factors (HIFs): determinants of cancer progression
Amelio, I., & Melino, G. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.04.007 · Cited by 152
Stromal integrin α11 regulates PDGFRβ signaling and promotes breast cancer progression
Primac, I., Maquoi, E., Blacher, S., Heljäsvaara, R., Deun, J. V., Smeland, H. Y., Canale, A., Louis, T., Stuhr, L. E. B., Sounni, N. E., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci125890 · Cited by 155
Current and Emerging Therapies in Metastatic Pancreatic Cancer
Manji, G. A., Olive, K. P., Saenger, Y. M., & Oberstein, P. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2319 · Cited by 145
TP53 mutations in epithelial ovarian cancer
Zhang, Y., Cao, L., Nguyen, D., & Lu, H. (2016) · Translational Cancer Research · doi:10.21037/tcr.2016.08.40 · Cited by 156
“Similarly, in a pancreatic cancer mouse model, mutant p53 can directly bind to p73, preventing p73-mediated inactivation of PDGFβ, driving an invasive and metastatic phenotype (52).”
BackgroundNagarajan, A. G., Dogra, S. K., Sun, L., Gandotra, N., Ho, T., Cai, G., Cline, G. W., Kumar, P., Cowles, R. A., & Wajapeyee, N. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.07.014 · Cited by 145
“Previous studies have shown that oncogenic KRAS mutations are necessary to initiate and maintain PDAC tumor growth (Bryant et al., 2014; Ying et al., 2012), and p53 mutations facilitate the metastatic progression of PDAC (Weissmueller et al., 2014).”
BackgroundInfluentialThe proprotein convertase furin in tumour progression
Jaaks, P., & Bernasconi, M. (2017) · International Journal of Cancer · doi:10.1002/ijc.30714 · Cited by 148
“Furthermore, autocrine PDGF signalling increases the metastatic potential of breast cancer and pancreatic cancer cells.(97,98) In diverse studies it has been shown that class III semaphorins are cleaved by furin or furin-like PCs, sometimes at multiple sites, however, the functional consequences of the processing step…”
BackgroundPfister, N. T., Fomin, V., Regunath, K., Zhou, J. Y., Zhou, W., Silwal‐Pandit, L., Freed-Pastor, W. A., Laptenko, O., Neo, S. P., Bargonetti, J., et al. (2015) · Genes & Development · doi:10.1101/gad.263202.115 · Cited by 149
“Interestingly, mutant p53 has been reported to stimulate additional receptor tyrosine kinases, including EGFR (Ludes-Meyers et al. 1996), IGF1R (Werner et al. 1996), MET (Muller et al. 2013), and PDGFRB (Weissmueller et al. 2014), all of which, along with VEGFR2, promote proproliferative signaling.”
BackgroundInfluentialSelf-citationPlatelet‐derived growth factor ( PDGF ) signalling in cancer: rapidly emerging signalling landscape
Farooqı, A. A., & Siddik, Z. H. (2015) · Cell Biochemistry and Function · doi:10.1002/cbf.3120 · Cited by 141
“Interestingly, the frequently occurring gain-of-function p53R172H and p53R273H mutants even induce PDGFRB, which may further promote the aggressive nature of such cancers.(4) Similarly, the p53 family member p73 can exist in the ΔNp73 isoform, which has been demonstrated in neuroblastoma to replace wild-type p53 on th…”
BackgroundEnhanced breast cancer progression by mutant p53 is inhibited by the circular RNA circ-Ccnb1
Fang, L., Du, W. W., Lyu, J., Dong, J., Zhang, C., Yang, W., He, A. T., Kwok, Y. S. S., Ma, J., Wu, N., et al. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0115-6 · Cited by 139
“It has been known that the p53 mutant cells express much higher levels of the mutant p53 [33].”
Amelio, I., Mancini, M., Petrova, V., Cairns, R. A., Вихрева, П. Н., Nicolai, S., Marini, A., Antonov, A. A., Quesne, J. P. C. L., Acevedo, J. D. B., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1808314115 · Cited by 144
How mutations shape p53 interactions with the genome to promote tumorigenesis and drug resistance
Stiewe, T., & Haran, T. E. (2018) · Drug Resistance Updates · doi:10.1016/j.drup.2018.05.001 · Cited by 143
Transcriptional Regulation by Wild-Type and Cancer-Related Mutant Forms of p53Preprint
Pfister, N. T., & Prives, C. L. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026054 · Cited by 146
“…2008; Lim et al. 2009), which can be mediated through mutant p53 interaction with Ets-2 (Do et al. 2012), increased migration (Adorno et al. 2009; Weissmueller et al. 2014), increased invasion through Matrigel (Muller et al. 2009, 2013), increased tumor inflammation (Scian et al. 2005), and…”
BackgroundInfluentialSelf-citationHashimoto, S., Furukawa, S., Hashimoto, A., Tsutaho, A., Fukao, A., Sakamura, Y., Parajuli, G., Onodera, Y., Otsuka, Y., Handa, H., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901765116 · Cited by 149
“Thus, it was enigmatic as to why PDGFR overexpression was a risk factor of PDACs (14), although most PDACs already have the KRAS oncogene.”
BackgroundInfluentialThe Function of the Mutant p53-R175H in Cancer
Chiang, Y.-T., Chien, Y., Lin, Y., Wu, H.-H., Lee, D., & Yu, Y. (2021) · Cancers · doi:10.3390/cancers13164088 · Cited by 127
“Pancreatic cancer p73 NF-YA, NF-YB, and NF-YC complex/PDGFRb [28]”
BackgroundInfluentialMaddalena, M., Mallel, G., Nataraj, N. B., Shreberk‐Shaked, M., Hassin, O., Mukherjee, S., Arandkar, S., Rotkopf, R., Kapsack, A., Lambiase, G., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2025631118 · Cited by 124
“For example, mutp53 can promote PDAC metastatic propensity by elevating the expression of platelet-derived growth factor receptor b (PDGFRb), which is achieved through the ability of mutp53 to bind and inhibit the p53-related p73 protein (51).”
BackgroundMutant p53 promotes tumor progression and metastasis by the endoplasmic reticulum UDPase ENTPD5
Vogiatzi, F., Brandt, D. T., Schneikert, J., Fuchs, J., Grikscheit, K., Wanzel, M., Pavlakis, E., Charles, J. P., Timofeev, O., Nist, A., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612711114 · Cited by 99
“In part, this is achieved by mutp53 transcriptionally up-regulating the expression of receptors (20), by suppressing receptor targeting miRNAs (40), or by enhancing receptor recycling (18, 21).”
BackgroundInfluentialGong, Z., Zhang, S., Zeng, Z., Wu, H., Yang, Q., Xiong, F., Shi, L., Yang, J., Zhang, W., Zhou, Y., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110674 · Cited by 110
“p53 participates in all steps of tumor initiation and development by regulating the expression of many downstream genes; thus, p53 is also an important candidate target for cancer gene therapy [16, 17].”
BackgroundWu, K., Zhang, X., Li, F., Xiao, D., Hou, Y., Zhu, S., Liu, D., Ye, X., Ye, M., Yang, J., et al. (2015) · Nature Communications · doi:10.1038/ncomms10131 · Cited by 109
Mutant p53 controls tumor metabolism and metastasis by regulating PGC-1αPreprint
Basu, S., Gnanapradeepan, K., Barnoud, T., Kung, C.-P., Tavecchio, M., Scott, J., Watters, A. K., Chen, Q., Kossenkov, A. V., & Murphy, M. E. (2018) · Genes & Development · doi:10.1101/gad.309062.117 · Cited by 111
“Inactivation of p73 bymutant p53 causes increased PDGF receptor β (PDGFRβ) signaling and metastasis (Weissmueller et al. 2014).”
BackgroundMutant p53: Multiple Mechanisms Define Biologic Activity in Cancer
Kim, M., Zhang, Y., & Lozano, G. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00249 · Cited by 113
“Mutant p53-dependent sequestration of p73 from an NF-Y complex permits this transcriptional complex to function at the platelet-derived growth factor β promoter, resulting in expression of PDGFRβ and a prometastatic phenotype (41).”
BackgroundClinical implications of miRNAs in the pathogenesis, diagnosis and therapy of pancreatic cancer
Rachagani, S., Macha, M. A., Heimann, N., Seshacharyulu, P., Haridas, D., Chugh, S., & Batra, S. K. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.10.020 · Cited by 107
“However, p53 can also have gain of function mutations that can increase cell proliferation and other tumorigenic traits; in this case miRNA against p53 can have beneficial effects [65,194,195].”
HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer
Stojanovic, N., Hassan, Z., Wirth, M., Wenzel, P., Beyer, M., Schäfer, C., Brand, P., Kroemer, A., Stauber, R. H., Schmid, R. M., et al. (2016) · Oncogene · doi:10.1038/onc.2016.344 · Cited by 109
Gain-of-Function (GOF) Mutant p53 as Actionable Therapeutic Target
Schulz‐Heddergott, R., & Moll, U. M. (2018) · Cancers · doi:10.3390/cancers10060188 · Cited by 108
NF-Y in cancer: Impact on cell transformation of a gene essential for proliferation
Gurtner, A., Manni, I., & Piaggio, G. (2016) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.12.005 · Cited by 104
Alexandrova, E. M., Mirza, S. A., Xu, S., Schulz‐Heddergott, R., Marchenko, N. D., & Moll, U. M. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.80 · Cited by 103
“In allografts, knockdown of mutp53 in Kras pancreatic cancer cells strongly reduces their metastatic ability.(9) Finally, in a conditional inactivatable (‘floxable’) autochthonous mouse model, ablation of the R248Q knockin allele extends survival by 37%, induces regression or stagnation of advanced tumors and strongly…”
BackgroundTargeting PDGF‐mediated recruitment of pericytes blocks vascular mimicry and tumor growth
Thijssen, V. L., Paulis, Y. W. J., Nowak-Sliwinska, P. M., Deumelandt, K., Hosaka, K., Soetekouw, P. M. M. B., Cîmpean, A. M., Raica, M., Pauwels, P., van den Oord, J. J., et al. (2018) · The Journal of Pathology · doi:10.1002/path.5152 · Cited by 103
“These findings extend the observations that interfering with PDGF signaling could provide therapeutic benefit for different cancer patients [36]; for example, for the treatment of patients with aggressive tumors that are refractory to angiostatic therapy.”
BackgroundTAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation
Amelio, I., Inoue, S., Markert, E. K., Levine, A. J., Knight, R. A., Mak, T. W., & Melino, G. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410609111 · Cited by 106
“Expression of mutant p53 disrupts the p73/NF-Y interaction, determining a PDGFRb-dependent metastatic potential of pancreatic cancer cells (27).”
BackgroundSelf-citationP53: A Guardian of Immunity Becomes Its Saboteur through Mutation
Agupitan, A. D., Neeson, P. J., Williams, S., Howitt, J. A., Haupt, S., & Haupt, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103452 · Cited by 111
“Moreover, Arf6 activation is facilitated by the platelet-derived growth factor (PDGF), a product of TLR4 signalling, and its β receptor (PDGFRβ), a direct target of mutant p53 [178,186,187].”
BackgroundNAT10 is upregulated in hepatocellular carcinoma and enhances mutant p53 activity
Li, Q., Liu, X., Jin, K., Lu, M., Zhang, C., Du, X., & Xing, B. (2017) · BMC Cancer · doi:10.1186/s12885-017-3570-4 · Cited by 98
Kong, B., Wu, W., Cheng, T., Schlitter, A. M., Qian, C., Bruns, P., Jian, Z., Jäger, C., Regel, I., Raulefs, S., et al. (2015) · Gut · doi:10.1136/gutjnl-2014-307616 · Cited by 97
Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine
Conway, J. R. W., Herrmann, D., Evans, T. J., Morton, J. P., & Timpson, P. (2018) · Gut · doi:10.1136/gutjnl-2018-316822 · Cited by 97
“42 145 146 Interest-ingly, one patient with PDAC who responded well to AZD2014 therapy in a phase I trial was found to have a PDGFR1A mutation, and this may present a novel biomarker for therapies aimed at PI3K pathway inhibition.”
Targeting the Oncogenic p53 Mutants in Colorectal Cancer and Other Solid Tumors
Li, H., Zhang, J., TONG, J. H. M., Chan, A. W. H., Yu, J. Q., Kang, W., & To, K. F. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20235999 · Cited by 100
“Blocking of PDGFR-β prevents cancer cell invasion and metastasis formation both in vitro and in vivo [63].”
BackgroundCell fate regulation governed by p53: Friends or reversible foes in cancer therapy
Song, B., Yang, P., & Zhang, S. (2024) · 癌症：英文版 · doi:10.1002/cac2.12520 · Cited by 103
Do Mutations Turn p53 into an Oncogene?
Pitolli, C., Wang, Y., Mancini, M., Shi, Y., Melino, G., & Amelio, I. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20246241 · Cited by 97
“In pancreatic cancer, mutant R172H p53 has been shown to interact with p73, blocking the interaction of p73 with NF-Y (nuclear transcription factor Y), which in turn induces the expression of PDGFRβ (platelet-derived growth factor receptor beta), which is important for maintaining a metastatic phenotype (Figure 2A) [9…”
BackgroundHuang, Y., Liu, N., Liu, J., Liu, Y., Zhang, C., Long, S., Luo, G., Zhang, L., & Zhang, Y. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1688951 · Cited by 94
“A murine model data of pancreatic cancer harboring a latent mutant p53-R175H have firmly established that mutant p53 promoted invasion and metastasis through activating cell-autonomous PDGF receptor β Signaling [28].”
BackgroundHitting cancers’ weak spots: vulnerabilities imposed by p53 mutation
Gurpinar, E., & Vousden, K. H. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.04.001 · Cited by 98
Liu, G., Wei, C., Yuan, S., Zhang, Z., Li, J., Zhang, L., Wang, G., & Fang, L. (2022) · Phytotherapy Research · doi:10.1002/ptr.7558 · Cited by 94
Vidaurre, S., Fitzpatrick, C. J., Burzio, V. A., Briones, M., Villota, C., Villegas, J., Echenique, J., Oliveira-Cruz, L., Araya, M., Borgna, V., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.558841 · Cited by 94
Mutant p53: One, No One, and One Hundred Thousand
Walerych, D., Lisek, K., & Sal, G. D. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00289 · Cited by 95
“model and cell lines Metastasis Imatinib (22)”
BackgroundInfluentialHeterogeneity of TP53 Mutations and P53 Protein Residual Function in Cancer: Does It Matter?
Monti, P., Menichini, P., Speciale, A., Cutrona, G., Fais, F., Taìana, E., Neri, A., Bomben, R., Gentile, M., Gattei, V., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.593383 · Cited by 98
Loizou, E., Banito, A., Livshits, G., Ho, Y.-J., Koche, R. P., Sánchez-Rivera, F. J., Mayle, A., Chen, C.-C., Kinalis, S., Bagger, F. O., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1391 · Cited by 88
“For example, although p53R172H can display GOF effects by promoting invasion and metastasis in a pancreatic cancer model, it is not required for the sustained proliferation of pancreatic cancer cells, at least in vitro (13).”
BackgroundSelf-citationMutant p53 oncogenic functions in cancer stem cells are regulated by WIP through YAP/TAZ
Escoll, M., Gargini, R., Cuadrado, A., Antón, I. M., & Wandosell, F. G. (2017) · Oncogene · doi:10.1038/onc.2016.518 · Cited by 92
Chen, K., Qian, W., Li, J., Jiang, Z., Cheng, L., Yan, B., Cao, J., Sun, L., Zhou, C., Lei, M., et al. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12116 · Cited by 92
“Somatic mutations in the p53 tumor suppressor gene are also frequent genetic events that drive PDAC progression (Weissmueller et al., 2014).”
BackgroundZehendner, C. M., Valasarajan, C., Werner, A., Boeckel, J., Bischoff, F. C., John, D., Weirick, T., Glaser, S.-F., Roßbach, O., Jaé, N., et al. (2020) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201910-2041oc · Cited by 89
“It has previously been reported that p53 is a major regulator of PDGFRb and that it downregulates PDGFRb expression (42, 43); conversely, mutants of p53 have been found to drive PDGF signaling in various malignant diseases (44).”
BackgroundWang, W., Friedland, S. C., Guo, B., O’Dell, M. R., Alexander, W. B., Whitney‐Miller, C. L., Agostini‐Vulaj, D., Huber, A. R., Myers, J. R., Ashton, J. M., et al. (2018) · Gut · doi:10.1136/gutjnl-2017-315541 · Cited by 96
Furth, N., Aylon, Y., & Oren, M. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.163 · Cited by 91
Marquardt, S., Solanki, M., Spitschak, A., Vera, J., & Pützer, B. M. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.06.006 · Cited by 87
Agostino, S. D., Valenti, F., Sacconi, A., Fontemaggi, G., Pallocca, M., Pulito, C., Ganci, F., Muti, P. C., Strano, S., & Blandino, G. (2018) · Theranostics · doi:10.7150/thno.22167 · Cited by 85
“To further validate the analysis performed in TGCA subgroups, we considered PDGFRB as a gene transcriptionally regulated by mutant p53 [46] and MDM2 as a bona-fide target of wild-type p53.”
Siolas, D., Vucic, E., Kurz, E., Hajdu, C. H., & Bar‐Sagi, D. (2020) · Cell Reports · doi:10.1016/j.celrep.2021.109578 · Cited by 82
“Neutrophil presence (Chao et al., 2016; Steele et al., 2016) and Trp53R172H gain-of-function mutation in tumor cells (Morton et al., 2010; Weissmueller et al., 2014) have been implicated independently in promoting metastasis in mouse models of PDAC.”
BackgroundLi, P., Zhang, D., Shen, L., Dong, K., Wu, M., Ou, Z., & Shi, D. (2016) · Scientific Reports · doi:10.1038/srep22831 · Cited by 84
Wadhwa, R., Nigam, N., Bhargava, P., Dhanjal, J. K., Goyal, S., Grover, A., Sundar, D., Ishida, Y., Terao, K., & Kaul, S. C. (2016) · Journal of Cancer · doi:10.7150/jca.15170 · Cited by 81
“It is a complex multi-step phenomenon and involves interplay of several factors that enable cancer cells to acquire invasiveness and intravasate into circulatory system, survive in the blood or lymph circulation, form microvasculature and extravasate to form tumor mass at distant organs [1-3].”
BackgroundMolecularly targeted therapies for p53-mutant cancers
Zhao, D., Tahaney, W. M., Mazumdar, A., Savage, M. I., & Brown, P. H. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2575-0 · Cited by 82
“A recent study demonstrated that PDGFRb signaling enhanced the expression of a GOF mutant p53 induced pancreatic cancer metastasis in PKC mice harboring one oncogenic allele of Kras and one allele of p53 [146].”
Bioinformatics analysis of the serine and glycine pathway in cancer cells
Antonov, A. V., Agostini, M., Morello, M., Minieri, M., Melino, G., & Amelio, I. (2014) · Oncotarget · doi:10.18632/oncotarget.2668 · Cited by 82
“Part of mp53 GOF is due to mp53 interaction and consequent repression of the siblings, p63/p73 [78–81], making this scenario much more complex.”
BackgroundEZH2 cooperates with gain‐of‐function p53 mutants to promote cancer growth and metastasis
Zhao, Y., Ding, L., Wang, D., Ye, Z., He, Y., Ma, L., Zhu, R., Pan, Y., Wu, Q., Pang, K., et al. (2019) · The EMBO Journal · doi:10.15252/embj.201899599 · Cited by 81
“Given that mutated p53 proteins are generally considered less drug-gable (Lehmann & Pietenpol, 2012), endeavor has been largely focused on targeting the downstream effectors of each individual GOF mutant of p53 (Adorno et al , 2009; Weissmueller et al , 2014; Zhu et al , 2015).”
Human MYC G-quadruplex: From discovery to a cancer therapeutic target
Wang, W., Hu, S., Gu, Y., Yan, Y., Stovall, D. B., Li, D., & Sui, G. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188410 · Cited by 79
Metadata
- Authors
- Weissmueller, S., Manchado, E., Saborowski, M., Morris, J. P., Wagenblast, E., Davis, C. A., Moon, S.-H., Pfister, N. T., Tschaharganeh, D. F., Kitzing, T., Aust, D., Markert, E. K., Wu, J., Grimmond, S. M., Pilarsky, C., Prives, C., Biankin, A. V., & Lowe, S. W.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Cold Spring Harbor Laboratory (US)
- Columbia University (US)
- Technische Universität Dresden (DE)
- Institute for Advanced Study (US)
- Garvan Institute of Medical Research (AU)
- The University of Queensland (AU)
- Corresponding author
- Lowe, Scott W.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 157
- Issue
- 2
- Pages
- 382-394
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4001090
- OpenAlex
- W2088441464
- Cited by
- 466
- References
- 61
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 16 · 2023: 42 · 2022: 42 · 2021: 54 · 2020: 43 · 2019: 32 · 2018: 48 · 2017: 59 · 2016: 50 · 2015: 33 · 2014: 18
- FWCI
- 25.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- Cancer Research UK (17263)
- National Cancer Institute (P01CA087497, P01CA129243, CA 013106, P01CA013106, P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- mutant p53, pancreatic cancer, metastasis, PDGF receptor beta, gain-of-function p53, cell invasion, prognostic factors, small molecule inhibitors, RNA interference, tumor suppressor inactivation
- MeSH terms
- Animals, Disease Models, Animal, Humans, Neoplasm Metastasis, Pancreatic Neoplasms, Tumor Suppressor Protein p53, Receptor, Platelet-Derived Growth Factor beta, Gene Expression Profiling, Carcinoma, Pancreatic Ductal, Mice
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.
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
