Knockdown of integrin α3β1 expression induces proliferation and migration of non-small cell lung cancer cells

Integrin alpha 3 beta 1 is expressed on many types of cancer cells and can regulate tumor growth and progression. In the present study, we examined the roles and molecular mechanism of integrin alpha 3 beta 1 in modulating cell proliferation and migration of p53-deficient non-small cell lung cancer (NSCLC) cells. Reduced expression of integrin alpha 3 by RNA silencing clearly induces cell proliferation and migration in H1299 cells, compared with those in control cells. Enhanced proliferation in integrin alpha 3-silenced cells is mediated by upregulation and nuclear localization of cyclin-dependent kinases, and these effects require the activation of Akt and ERK as evidenced by treatment with LY294002 and PD98059, respectively. Furthermore, suppression of integrin alpha 3 expression induces the expression of nuclear factor-kappa B and Bcl-2 as well as epidermal growth factor receptor, which are positively correlated with cell proliferation and survival. In contrast, increase in cell migration of integrin alpha 3-silenced cells is found to be independent of Akt or ERK signaling pathways. Collectively, these findings suggest that integrin alpha 3 beta 1 plays pivotal roles in regulating cell proliferation and migration that enhance the invasive type of p53-deficient NSCLC cells.