Kindlin 2 forms a transcriptional complex with β-catenin and TCF4 to enhance Wnt signalling
Kindlin 2 forms a transcriptional complex with β-catenin and TCF4 to enhance Wnt signalling
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DOI：
10.1038/embor.2012.88
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发表时间：
2012-08-01
期刊：
影响因子：
7.7
通讯作者：
Zhang, Hongquan
中科院分区：
文献类型：
--
作者：
Yu, Yu;Wu, Junzhou;Zhang, Hongquan
Kindlin 2作为黏着斑蛋白，控制整合素活化。然而，Kindlin 2与癌症相关信号通路的关联尚不清楚。在这里，我们确定了Kindlin 2和活性β-连环蛋白之间新的直接相互作用。重要的是，Kindlin 2与β-连环蛋白和TCF 4形成三重复合物。从机制上讲，Kindlin 2选择性地增强β-连环蛋白对Wnt靶基因Axin 2的占据并增强Axin 2基因表达。在功能上，β-连环蛋白-Axin 2-Snail级联是Kindlin 2诱导的肿瘤细胞侵袭所必需的。我们的数据表明，Kindlin 2是Wnt信号传导的一种新调节因子，为Kindlin 2在癌症进展中的作用提供了一种机制性见解。
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 beta-catenin. Importantly, Kindlin 2 forms a tripartite complex with beta-catenin and TCF4. Mechanistically, Kindlin 2 selectively strengthens the occupancy of beta-catenin on the Wnt target gene Axin2 and enhances Axin2 gene expression. Functionally, the beta-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.