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LYN Is a Mediator of Epithelial-Mesenchymal Transition and a Target of Dasatinib in Breast Cancer
DC Field | Value | Language |
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dc.contributor.author | Choi, Yoon-La | - |
dc.contributor.author | Melanie Bocanegra | - |
dc.contributor.author | Kwon, Mi Jeong | - |
dc.contributor.author | Shin, Young Kee | - |
dc.contributor.author | Nam, Seok Jin | - |
dc.contributor.author | Yang, Jung-Hyun | - |
dc.contributor.author | Jessica Kao | - |
dc.contributor.author | Andrew K. Godwin | - |
dc.contributor.author | Jonathan R. Pollack | - |
dc.date.accessioned | 2011-07-05T09:00:10Z | - |
dc.date.available | 2011-07-05T09:00:10Z | - |
dc.date.issued | 2010-03 | - |
dc.identifier.citation | Cancer Res; Vol.70(6); pp.2296–2306 | en |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://hdl.handle.net/10371/73455 | - |
dc.description.abstract | Epithelial-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is considered a key process driving tumor cell invasiveness and metastasis. Using breast cancer cell lines as a model system, we sought to discover gene expression signatures of EMT with clinical and mechanistic relevance. A supervised comparison of epithelial and mesenchymal breast cancer lines defined a 200-gene EMT signature that was prognostic across multiple breast cancer cohorts. The immunostaining of LYN, a top-ranked EMT signature gene and Src-family tyrosine kinase, was associated with significantly shorter overall survival (P = 0.02) and correlated with the basal-like (triple-negative) phenotype. In mesenchymal breast cancer lines, RNAi-mediated knockdown of LYN inhibited cell migration and invasion, but not proliferation. Dasatinib, a dual-specificity tyrosine kinase inhibitor, also blocked invasion (but not proliferation) at nanomolar concentrations that inhibit LYN kinase activity, suggesting that LYN is a likely target and that invasion is a relevant end point for dasatinib therapy. Our findings define a prognostically relevant EMT signature in breast cancer and identify LYN as a mediator of invasion and a possible new therapeutic target (and theranostic marker for dasatinib response), with particular relevance to clinically aggressive basal-like breast cancer. | en |
dc.language.iso | en | en |
dc.publisher | Cancer Research | en |
dc.title | LYN Is a Mediator of Epithelial-Mesenchymal Transition and a Target of Dasatinib in Breast Cancer | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 최윤라 | - |
dc.contributor.AlternativeAuthor | 권미정 | - |
dc.contributor.AlternativeAuthor | 신영기 | - |
dc.contributor.AlternativeAuthor | 남석진 | - |
dc.contributor.AlternativeAuthor | 양정현 | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-09-3141 | - |
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- College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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