LYN Is a Mediator of Epithelial-Mesenchymal Transition and a Target of Dasatinib in Breast Cancer
- Authors
- Choi, YL[Choi, Yoon-La]; Bocanegra, M[Bocanegra, Melanie]; Kwon, MJ[Kwon, Mi Jeong]; Shin, YK[Shin, Young Kee]; Nam, SJ[Nam, Seok Jin]; Yang, JH[Yang, Jung-Hyun]; Kao, J[Kao, Jessica]; Godwin, AK[Godwin, Andrew K.]; Pollack, JR[Pollack, Jonathan R.]
- Issue Date
- 15-Mar-2010
- Publisher
- AMER ASSOC CANCER RESEARCH
- Citation
- CANCER RESEARCH, v.70, no.6, pp.2296 - 2306
- Indexed
- SCIE
SCOPUS
- Journal Title
- CANCER RESEARCH
- Volume
- 70
- Number
- 6
- Start Page
- 2296
- End Page
- 2306
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/74692
- DOI
- 10.1158/0008-5472.CAN-09-3141
- ISSN
- 0008-5472
- 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. Cancer Res; 70(6); 2296-306. (C) 2010 AACR.
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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