Alteration in Metastasis Potential and Gene Expression in Human Lung Cancer Cell Lines by ITGB8 Silencing

Abstract

Lung cancer is the leading cause of cancer death in the world and metastasis is an essential aspect of lung cancer progression. ITGB8 has been implicated in metastasis of human tumors. However, the molecular mechanism by which ITGB8 is involved in tumor metastasis is still unclear. In this study, we compared the gene expression profiles of human lung cancer cell lines A549 and PC9 by ITGB8 gene silencing with that of parent cells and negative control cells to comprehensively investigate ITGB8-mediated changes with respect to the metastatic potential and gene expression of human lung cancer cell lines. Our results showed that ITGB8 silencing cells exhibited significant cell cycle arrest and less adhesion and invasion abilities. We confirmed by Western blot, ELISA, and real-time PCR that the expression of metastasis-related genes CXCL1, CXCL2, CXCL5, MMP-2, and MMP-9 were significantly decreased while that of E-Cadherin and cystatin B were dramatically increased in A549- and PC9-ITGB8 silencing cells. Furthermore, silencing of ITGB8 caused Snail and NF-κB transcriptional activation, and MEK and Akt phosphorylation level changes in lung cancer cell lines. Our results indicated that ITGB8 may play an important role in metastasis of human lung cancer cells. The ITGB8 silencing may change the lung cancer cells to a less invasive phenotype through alteration in the expression of metastasis-related genes. © 2012 Wiley Periodicals, Inc.