| Literature DB >> 21376233 |
Tingting Sun1, Nicola Aceto, Kristen L Meerbrey, Jessica D Kessler, Chunshui Zhou, Ilenia Migliaccio, Don X Nguyen, Natalya N Pavlova, Maria Botero, Jian Huang, Ronald J Bernardi, Earlene Schmitt, Guang Hu, Mamie Z Li, Noah Dephoure, Steven P Gygi, Mitchell Rao, Chad J Creighton, Susan G Hilsenbeck, Chad A Shaw, Donna Muzny, Richard A Gibbs, David A Wheeler, C Kent Osborne, Rachel Schiff, Mohamed Bentires-Alj, Stephen J Elledge, Thomas F Westbrook.
Abstract
Among breast cancers, triple-negative breast cancer (TNBC) is the most poorly understood and is refractory to current targeted therapies. Using a genetic screen, we identify the PTPN12 tyrosine phosphatase as a tumor suppressor in TNBC. PTPN12 potently suppresses mammary epithelial cell proliferation and transformation. PTPN12 is frequently compromised in human TNBCs, and we identify an upstream tumor-suppressor network that posttranscriptionally controls PTPN12. PTPN12 suppresses transformation by interacting with and inhibiting multiple oncogenic tyrosine kinases, including HER2 and EGFR. The tumorigenic and metastatic potential of PTPN12-deficient TNBC cells is severely impaired upon restoration of PTPN12 function or combined inhibition of PTPN12-regulated tyrosine kinases, suggesting that TNBCs are dependent on the proto-oncogenic tyrosine kinases constrained by PTPN12. Collectively, these data identify PTPN12 as a commonly inactivated tumor suppressor and provide a rationale for combinatorially targeting proto-oncogenic tyrosine kinases in TNBC and other cancers based on their profile of tyrosine-phosphatase activity.Entities:
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Year: 2011 PMID： 21376233 PMCID： PMC6014607 DOI： 10.1016/j.cell.2011.02.003
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582