Kindlin 2 forms a transcriptional complex with ?-catenin and TCF4 to enhance Wnt signalling.
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 ?-catenin. Importantly, Kindlin 2 forms a tripartite complex with ?-catenin and TCF4. Mechanistically, Kindlin 2 ... selectively strengthens the occupancy of ?-catenin on the Wnt target gene Axin2 and enhances Axin2 gene expression. Functionally, the ?-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.
Mesh Terms:
Axin Protein, Blotting, Western, Cell Line, Epithelial-Mesenchymal Transition, Humans, Membrane Proteins, Multiprotein Complexes, Neoplasm Invasiveness, Neoplasm Proteins, Protein Binding, Protein Stability, Transcription Factor 7-Like 2 Protein, Transcription, Genetic, Wnt Signaling Pathway, beta Catenin
Axin Protein, Blotting, Western, Cell Line, Epithelial-Mesenchymal Transition, Humans, Membrane Proteins, Multiprotein Complexes, Neoplasm Invasiveness, Neoplasm Proteins, Protein Binding, Protein Stability, Transcription Factor 7-Like 2 Protein, Transcription, Genetic, Wnt Signaling Pathway, beta Catenin
EMBO Rep
Date: Aug. 01, 2012
PubMed ID: 22699938
View in: Pubmed Google Scholar
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