dc.contributor.author | Sun, Tingting | |
dc.contributor.author | Aceto, Nicola | |
dc.contributor.author | Meerbrey, Kristen L. | |
dc.contributor.author | Kessler, Jessica D. | |
dc.contributor.author | Zhou, Chunshui | |
dc.contributor.author | Migliaccio, Ilenia | |
dc.contributor.author | Nguyen, Don X. | |
dc.contributor.author | Pavlova, Natalya N. | |
dc.contributor.author | Botero, Maria | |
dc.contributor.author | Huang, Jian | |
dc.contributor.author | Bernardi, Ronald J. | |
dc.contributor.author | Schmitt, Earlene | |
dc.contributor.author | Hu, Guang | |
dc.contributor.author | Li, Mamie Z. | |
dc.contributor.author | Dephoure, Noah | |
dc.contributor.author | Rao, Mitchell | |
dc.contributor.author | Creighton, Chad J. | |
dc.contributor.author | Hilsenbeck, Susan G. | |
dc.contributor.author | Shaw, Chad A. | |
dc.contributor.author | Muzny, Donna | |
dc.contributor.author | Gibbs, Richard A. | |
dc.contributor.author | Wheeler, David A. | |
dc.contributor.author | Osborne, C. Kent | |
dc.contributor.author | Schiff, Rachel | |
dc.contributor.author | Bentires-Alj, Mohamed | |
dc.contributor.author | Westbrook, Thomas F. | |
dc.contributor.author | Elledge, Stephen | |
dc.contributor.author | Gygi, Steven | |
dc.date.accessioned | 2019-08-19T08:32:15Z | |
dc.date.issued | 2011-03 | |
dc.identifier.citation | Sun, Tingting, Nicola Aceto, Kristen L. Meerbrey, Jessica D. Kessler, Chunshui Zhou, Ilenia Migliaccio, Don X. Nguyen, et al. 2011. “Activation of Multiple Proto-Oncogenic Tyrosine Kinases in Breast Cancer via Loss of the PTPN12 Phosphatase.” Cell 144 (5): 703–18. https://doi.org/10.1016/j.cell.2011.02.003. | en_US |
dc.identifier.issn | 0092-8674 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:41200881 | * |
dc.description.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. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Elsevier BV | en_US |
dash.license | META_ONLY | |
dc.subject | General Biochemistry, Genetics and Molecular Biology | en_US |
dc.title | Activation of Multiple Proto-oncogenic Tyrosine Kinases in Breast Cancer via Loss of the PTPN12 Phosphatase | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | Cell | en_US |
dash.depositing.author | Elledge, Stephen | |
dc.date.available | 2019-08-19T08:32:15Z | |
dash.workflow.comments | 1Science Serial ID 19935 | en_US |
dc.identifier.doi | 10.1016/j.cell.2011.02.003 | |
dc.source.journal | Cell | |
dash.source.volume | 144;5 | |
dash.source.page | 703-718 | |
dash.contributor.affiliated | Elledge, Stephen | |
dash.contributor.affiliated | Gygi, Steven | |