Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor β signaling Journal Article

   

Authors:	Weissmueller, S.; Manchado, E.; Saborowski, M.; Morris, J. P. 4th; 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.
Article Title:	Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor β signaling
Abstract:	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. © 2014 Elsevier Inc.
Journal Title:	Cell
Volume:	157
Issue:	2
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	2014-04-10
Start Page:	382
End Page:	394
Language:	English
DOI:	10.1016/j.cell.2014.01.066
PROVIDER:	scopus
PMCID:	PMC4001090
PUBMED:	24725405
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84898614449&partnerID=40&md5=b0992433871615c11a1cb619403879ab
Notes:	Export Date: 1 May 2014 -- CODEN: CELLB -- Source: Scopus

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