Kindlin 2 promotes breast cancer invasion via epigenetic silencing of the microRNA200 gene family.
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.
['Yu|Yu|Y|', 'Wu|Junzhou|J|', 'Guan|Lizhao|L|', 'Qi|Lihua|L|', 'Tang|Yan|Y|', 'Ma|Bo|B|', 'Zhan|Jun|J|', 'Wang|Yunling|Y|', 'Fang|Weigang|W|', 'Zhang|Hongquan|H|']
D000818:Animals D001943:Breast Neoplasms D045744:Cell Line, Tumor D018899:CpG Islands D004248:DNA (Cytosine-5-)-Methyltransferases D019175:DNA Methylation D000090205:DNA Methyltransferase 3A D005260:Female D020868:Gene Silencing D006801:Humans D008565:Membrane Proteins D051379:Mice D016513:Mice, SCID D035683:MicroRNAs D009361:Neoplasm Invasiveness D009363:Neoplasm Proteins
Kindlins breast cancer DNA methyltransferase MicroRNA-200 family