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.
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“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]
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Self-citationCore Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
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“Notably, the c-KIT and BCR-ABL kinases have not been linked to PDAC development (Jones et al., 2008).”
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“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
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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
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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
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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
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