Loss of Med1/TRAP220 promotes the invasion and metastasis of human non-small-cell lung cancer cells by modulating the expression of metastasis-related genes

Cancer Lett. 2012 Aug 28;321(2):195-202. doi: 10.1016/j.canlet.2012.02.009. Epub 2012 Feb 14.

Abstract

Med1/TRAP220 is an essential component of the TRAP/Mediator complex. In this study, we present a novel function of Med1 in human non-small-cell lung cancer (NSCLC) progression. We found that the loss of Med1 expression was strongly associated with increased rates of invasion and metastasis in NSCLC patients. Consistent with lung cancer patient data, the knockdown of Med1 in NSCLC cell lines led to an increase in cell migration and invasion. Med1-depleted cells displayed an increase in metastasis in a xenograft tumor model and in an in vivo metastasis assay. Moreover, a microarray analysis revealed that the mRNA levels of the metastasis-related genes uPAR, ID2, ID4, PTP4A1, PKP3, TGM2, PLD1, TIMP2, RGS2, and HOXA4 were altered upon Med1 knockdown. Collectively, these results suggest that the loss of Med1 increases the invasive potential of human NSCLC cells by modulating the expression of metastasis-related genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Gene Expression
  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mediator Complex Subunit 1 / genetics*
  • Mediator Complex Subunit 1 / metabolism
  • Mice
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Metastasis / genetics*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • MED1 protein, human
  • Mediator Complex Subunit 1
  • RNA, Messenger
  • Transcription Factors