Novel focal adhesion protein kindlin-2 promotes the invasion of gastric cancer cells through phosphorylation of integrin β1 and β3.

We have found that the expression of the novel focal adhesion protein kindlin-2 had a significant positive correlation with poor survival in gastric cancer. However, the mechanism by which kindlin-2 acts in gastric cancer warrants further evaluation. Kindlin-2 mRNA expression in gastric cancer cell lines was measured by realtime RT-PCR under normal and hypoxic conditions. Cell proliferation, apoptosis, cell cycle, tumor adhesion, cell invasion ability, and phosphorylation of integrin β1 and β3 proteins were measured to assess the influence of kindlin-2 on the malignant behavior of gastric cancer cells. Kindlin-2 mRNA expression was highest in the distant metastasis gastric cancer cell line Hs-746T. Cell proliferation, adhesion with endothelium and collagen IV, invasion rate, and angiogenesis genes expression, as well as phosphorylation of integrin β1 and β3 in Hs-746T, were decreased significantly after kindlin-2 downregulation, but there was no change in apoptosis and cell cycle. Kindlin-2 might promote the invasion of gastric cancer cells through enhancing proliferation and adhesion by the phosphorylation of integrin β1 and β3.