tion of integrin a2b1 in cancer cell invasion and metastasis

In our research, increased expression of both the a2 and b1 sub-units was observed in IR cells, suggesting an essential role of integrin a2b1 within the increased invasiveness after IR therapy. Apparently, the mRNA level of the integrin a1 subunit reduces in IR cells. A few studies noted that integrin enzalutamide a1b1 and a2b1 might play diverse roles in lots of aspects, such as collagen and collagenase gene expression, and EGFR service, which suggests that decreased expression of a1 integrin might also favor the increased invasiveness of IR cells. Along with integrin a2b1, a growth factor receptor that is frequently aberrant in NSCLC, EGFR, was found overexpressed and activated in IR cells. Our provided new evidence for the importance of EGFR inhibition, though it has been demonstrated that advantages of EGFR inhibition on radiosensitization Organism of cancer cells is mainly due to a decrease in cell proliferation and clonogenic survival. We showed here that EGFR expression and activation were increased in lung cancer cells that survived IR, and this level was required for their increased invasiveness. The tasks of EGFR and integrin a2b1 within the activation of Akt were observed through its damaged activation after inhibition of EGFR or functional restriction of integrin a2b1. On the other hand, inhibition of PI3K/Akt resulted in similar spherical morphology and partially blocked the EGFR and integrin a2b1 mediated invasion in IR cells. In contrast, the invasiveness of IR cells and elongated phenotype were not dependent on MEK/Erk1/2, though Erk1/2 was also showed activation in IR cells. Alternatively, enhanced Erk1/2 activation in the presence of the PI3K inhibitor suggests the existence of a compensatory mechanism between PI3K/Akt and MEK/Erk1/2 signaling pathways, which has been implicated in other studies. Moreover, Erk1/2 activation was influenced by activation of integrin a2b1, but not EGFR, which can be BMN 673 possibly associated with the survival of IR cells upon the strain of IR, as other studies have suggested. Nevertheless, direct inhibition of MEK/Erk1/2 might cause unwanted outcomes, such as augmenting EGFRdriven motility demonstrated in prostate cancer. Recent work showed crosstalk between signaling pathways involving EGFR and integrins in cancer progression. For instance, EGFR at cell cell contact websites and physical affiliation between integrin a2b1 was reported in A431 cells with unknown biological function. Appearance of the integrin a2 subunit was selectively increased upon EGF mediated EGFR activation in both A431 cells and A549 cells. b1 integrin silenced cells show defective service of the EGFR signaling cascade, resulting in decreased in vitro growth, enhanced sensitivity to cisplatin and gefitinib, reduced migration, and unpleasant behavior of A549 cells. These observations support our theory that integrin a2b1 and EGFR may coordinately regulate signal transduction responsible for IR cell invasion.