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

Mol Carcinog. 2012 Jul;51(7):522-34. doi: 10.1002/mc.20815. Epub 2011 Jul 7.

Abstract

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.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation*
  • ErbB Receptors / metabolism*
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • RNA, Small Interfering
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • ERRFI1 protein, human
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • ErbB Receptors