| Literature DB >> 29017057 |
Stephano S Mello1, Liz J Valente1, Nitin Raj1, Jose A Seoane2, Brittany M Flowers1, Jacob McClendon1, Kathryn T Bieging-Rolett1, Jonghyeob Lee3, Danton Ivanochko4, Margaret M Kozak1, Daniel T Chang5, Teri A Longacre6, Albert C Koong5, Cheryl H Arrowsmith4, Seung K Kim7, Hannes Vogel6, Laura D Wood8, Ralph H Hruban8, Christina Curtis9, Laura D Attardi10.
Abstract
The p53 transcription factor is a critical barrier to pancreatic cancer progression. To unravel mechanisms of p53-mediated tumor suppression, which have remained elusive, we analyzed pancreatic cancer development in mice expressing p53 transcriptional activation domain (TAD) mutants. Surprisingly, the p5353,54 TAD2 mutant behaves as a "super-tumor suppressor," with an enhanced capacity to both suppress pancreatic cancer and transactivate select p53 target genes, including Ptpn14. Ptpn14 encodes a negative regulator of the Yap oncoprotein and is necessary and sufficient for pancreatic cancer suppression, like p53. We show that p53 deficiency promotes Yap signaling and that PTPN14 and TP53 mutations are mutually exclusive in human cancers. These studies uncover a p53-Ptpn14-Yap pathway that is integral to p53-mediated tumor suppression. CrownEntities:
Keywords: Hippo pathway; Ptpn14; YAP; mouse model; p53; pancreas cancer; transactivation domain; tumor suppressor
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Year: 2017 PMID： 29017057 PMCID： PMC5659188 DOI： 10.1016/j.ccell.2017.09.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743