Kindlin 2 forms a transcriptional complex with ß-catenin and TCF4 to enhance Wnt signalling.

ABSTRACT

Kindlin 2, as a focal adhesion protein, controls integrin activation. However, the association of Kindlin 2 with cancer-related signalling pathways is unknown. Here we identified a new direct interaction between Kindlin 2 and the active ß-catenin. Importantly, Kindlin 2 forms a tripartite complex with ß-catenin and TCF4. Mechanistically, Kindlin 2 selectively strengthens the occupancy of ß-catenin on the Wnt target gene Axin2 and enhances Axin2 gene expression. Functionally, the ß-catenin-Axin2-Snail cascade is required for Kindlin 2-induced tumour cell invasion. Our data indicate that Kindlin 2 is a new regulator of Wnt signalling, providing a mechanistic insight into the role of Kindlin 2 in cancer progression.