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MRTF ‐ A and STAT 3 promote MDA ‐ MB ‐231 cell migration via hypermethylating BRSM 1
Author(s) -
Xing WenJing,
Liao XingHua,
Wang Nan,
Zhao DongWei,
Zheng Li,
Zheng DeLiang,
Dong Jian,
Zhang TongCun
Publication year - 2015
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1362
Subject(s) - cell migration , stat3 , cancer research , metastasis , transcription factor , chemistry , biology , microbiology and biotechnology , cell , cancer , signal transduction , gene , biochemistry , genetics
Breast cancer is the leading cause of cancer death in women worldwide which is closely related to metastasis. But the exact molecular mechanism of metastasis is still not fully understood. We now report that both MRTF‐A and STAT3 play important roles in migration of MDA‐MB‐231 breast cancer cells. Moreover, MRTF‐A and STAT3 synergistically increased MDA‐MB‐231 cell migration by promoting the expression of migration markers urokinase‐type plasminogen activator (uPA) and osteopontin (OPN) and inhibiting the expression of breast cancer metastasis suppressor 1 (BRMS1). Luciferase reporter assays demonstrated that MRTF‐A and STAT3 do not affect transcription of the BRMS1 promoter. Instead, we identified a newly molecular mechanism by which MRTF‐A and STAT3 synergistically controlled MDA‐MB‐231 cell migration by recruiting DNMT1 to hypermethylate the promoter of BRMS1 and thus affect the expression of BRMS1. Interestingly, physical interaction between MRTF‐A and STAT3 synergistically promotes the transactivity of DNMT1 by binding to the GAS element within the DNMT1 promoter. Our data thus provide important and novel insights into the roles of MRTF‐A and STAT3 in regulating MDA‐MB‐231 cell migration. © 2015 IUBMB Life, 67(3):202–217, 2015