Downregulation of Mig-6 in nonsmall-cell lung cancer is associated with EGFR signaling.

Downregulation of Mig-6 expression has been implicated in several human cancers and its loss can lead to prolonged activation of EGFR and carcinogenesis. The present study aimed to investigate the clinical significance of loss of Mig-6 expression in nonsmall-cell lung cancer (NSCLC) and the biological functions of Mig-6 in NSCLC cell lines. Mig-6 expression was downregulated in 47/91 (51.6%) cases of NSCLC that were examined. Mig-6 downregulation significantly correlated with poor differentiation (P = 0.0131), histological type (P = 0.0021), and EGFR expression (P = 0.003). In addition, knockdown of Mig-6 expression in H1299 and BE1 cells promoted EGF-induced tumor cell proliferation and migration. Furthermore, Mig-6 knockdown led to a significant increase in phospho-AKT, phospho-ERK, phospho-EGFR as well as MMP-2 and MMP-9 levels. These results indicate that downregulated Mig-6 in NSCLC tissues may serve as a new marker that can predict the activation of EGFR signaling pathway.