IQGAP3 promotes EGFR-ERK signaling and the growth and metastasis of lung cancer cells

PLoS One. 2014 May 21;9(5):e97578. doi: 10.1371/journal.pone.0097578. eCollection 2014.

Abstract

Proteins of the IQGAP family display complicated and often contradictory activities in tumorigenesis. IQGAP1 has well documented oncogenic potential and IQGAP2 has putative tumor-suppressive function. IQGAP3 is the latest addition to this family and its role in cancer development remains to be defined. Here we demonstrate IQGAP3 expression is markedly increased in lung cancer tissues at both mRNA and protein levels. Overexpression of IQGAP3 promoted tumor cell growth, and migration and invasion, whereas knockdown of IQGAP3 exhibited opposite effects. Moreover, suppression of IQGAP3 in a lung cancer cell line caused a reduction in the tumorigenicity of these cells in lung tissue after intravenous injection. Furthermore, we showed that IQGAP3 is able to interact with ERK1 and enhance its phosphorylation following treatment with EGF. These data suggest that IQGAP3 may contribute to the pathogenesis of lung cancer by modulating EGFR-ERK signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • ErbB Receptors / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • GTPase-Activating Proteins / deficiency
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phosphorylation
  • Signal Transduction*
  • Up-Regulation

Substances

  • GTPase-Activating Proteins
  • IQGAP3 protein, human
  • ErbB Receptors
  • Extracellular Signal-Regulated MAP Kinases

Grants and funding

This work received support from the National Basic Research Program of China (2011CB946103), National Natural Sciences Foundation of China (31330025 and 30830091), Beijing Municipal Natural Science Foundation (7122104) and the 111 Project of China (B07001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.