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Int J Cancer. 2013 Sep 15;133(6):1368-79. doi: 10.1002/ijc.28151. Epub 2013 Apr 11.

Kindlin 2 promotes breast cancer invasion via epigenetic silencing of the microRNA200 gene family.

Author information

1
Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education of China, Peking University Health Science Center, Beijing, 100191, China.

Abstract

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.

KEYWORDS:

DNA methyltransferase; Kindlins; MicroRNA-200 family; breast cancer

PMID:
23483548
DOI:
10.1002/ijc.28151
[Indexed for MEDLINE]
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