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LYN Is a Mediator of Epithelial-Mesenchymal Transition and a Target of Dasatinib in Breast Cancer

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dc.contributor.authorChoi, Yoon-La-
dc.contributor.authorMelanie Bocanegra-
dc.contributor.authorKwon, Mi Jeong-
dc.contributor.authorShin, Young Kee-
dc.contributor.authorNam, Seok Jin-
dc.contributor.authorYang, Jung-Hyun-
dc.contributor.authorJessica Kao-
dc.contributor.authorAndrew K. Godwin-
dc.contributor.authorJonathan R. Pollack-
dc.date.accessioned2011-07-05T09:00:10Z-
dc.date.available2011-07-05T09:00:10Z-
dc.date.issued2010-03-
dc.identifier.citationCancer Res; Vol.70(6); pp.2296–2306en
dc.identifier.issn0008-5472-
dc.identifier.urihttps://hdl.handle.net/10371/73455-
dc.description.abstractEpithelial-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.isoenen
dc.publisherCancer Researchen
dc.titleLYN Is a Mediator of Epithelial-Mesenchymal Transition and a Target of Dasatinib in Breast Canceren
dc.typeArticleen
dc.contributor.AlternativeAuthor최윤라-
dc.contributor.AlternativeAuthor권미정-
dc.contributor.AlternativeAuthor신영기-
dc.contributor.AlternativeAuthor남석진-
dc.contributor.AlternativeAuthor양정현-
dc.identifier.doi10.1158/0008-5472.CAN-09-3141-
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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