| Title |
A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer
|
|---|---|
| Published in |
Cancer Cell, October 2017
|
| DOI | 10.1016/j.ccell.2017.09.007 |
| Pubmed ID | |
| Authors |
Stephano S. Mello, Liz J. Valente, Nitin Raj, Jose A. Seoane, Brittany M. Flowers, Jacob McClendon, Kathryn T. Bieging-Rolett, Jonghyeob Lee, Danton Ivanochko, Margaret M. Kozak, Daniel T. Chang, Teri A. Longacre, Albert C. Koong, Cheryl H. Arrowsmith, Seung K. Kim, Hannes Vogel, Laura D. Wood, Ralph H. Hruban, Christina Curtis, Laura D. Attardi |
| 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 p53(53,54) 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. |
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X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 13 | 41% |
| United Kingdom | 2 | 6% |
| Switzerland | 1 | 3% |
| Kuwait | 1 | 3% |
| Australia | 1 | 3% |
| Spain | 1 | 3% |
| Canada | 1 | 3% |
| Belgium | 1 | 3% |
| Russia | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 9 | 28% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 17 | 53% |
| Scientists | 12 | 38% |
| Practitioners (doctors, other healthcare professionals) | 2 | 6% |
| Science communicators (journalists, bloggers, editors) | 1 | 3% |
Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 236 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 44 | 19% |
| Student > Ph. D. Student | 39 | 17% |
| Student > Bachelor | 24 | 10% |
| Student > Master | 24 | 10% |
| Student > Doctoral Student | 17 | 7% |
| Other | 30 | 13% |
| Unknown | 58 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 83 | 35% |
| Agricultural and Biological Sciences | 35 | 15% |
| Medicine and Dentistry | 24 | 10% |
| Immunology and Microbiology | 7 | 3% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 2% |
| Other | 16 | 7% |
| Unknown | 66 | 28% |