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Kindlin 2 promotes breast cancer invasion via epigenetic silencing of the microRNA200 gene family
Author(s) -
Yu Yu,
Wu Junzhou,
Guan Lizhao,
Qi Lihua,
Tang Yan,
Ma Bo,
Zhan Jun,
Wang Yunling,
Fang Weigang,
Zhang Hongquan
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28151
Subject(s) - gene silencing , epigenetics , microrna , wnt signaling pathway , psychological repression , biology , cancer research , breast cancer , dna methylation , microbiology and biotechnology , cpg site , cancer , signal transduction , gene , gene expression , genetics
Kindlin 2, as a focal adhesion protein, controls integrin activation and regulates Wnt signaling in an integrin‐binding independent manner. However, the association of Kindlin 2 with cancer‐related microRNAs is unknown. Here, we report that Kindlin 2 markedly downregulates the expression of miR‐200 family by inducing CpG island hypermethylation. Mechanistically, Kindlin 2 forms a complex with DNMT3A in the cell nucleus and the two proteins co‐occupy the promoter of miRNA‐200b. Functionally, repression of miR‐200b is required for Kindlin 2‐induced breast cancer cell invasion and tumor formation. Our data indicate that Kindlin 2 plays a novel role in epigenetic repression of miR‐200 family, a mechanism that promotes breast cancer invasion.