Kindlin 2 forms a transcriptional complex with β-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 β-catenin. Importantly, Kindlin 2 forms a tripartite complex with β-catenin and TCF4. Mechanistically, Kindlin 2 selectively strengthens the occupancy of β-catenin on the Wnt target gene Axin2 and enhances Axin2 gene expression. Functionally, the β-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.
Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, #38 Xue Yuan Road, Beijing 100191, China.
Yu
Y
Yu
Junzhou
J
Wu
Yunling
Y
Wang
Ting
T
Zhao
Bo
B
Ma
Yuqing
Y
Liu
Weigang
W
Fang
Wei-Guo
WG
Zhu
Hongquan
H
Zhang
D060466:Axin Protein / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D055550:Protein Stability; D058118:Transcription Factor 7-Like 2 Protein / Q000378:metabolism*; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism*
C491761:AXIN2 protein, human; D060466:Axin Protein; C477322:FERMT3 protein, human; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin