GCF2/LRRFIP1 promotes colorectal cancer metastasis and liver invasion through integrin-dependent RhoA activation

Cancer Lett. 2012 Dec 1;325(1):99-107. doi: 10.1016/j.canlet.2012.06.012. Epub 2012 Jun 28.

Abstract

The precise relationship between GCF2 expression and carcinogenesis has not yet been established. To clarify the metastatic potential of GCF2 in colorectal cancer, HT-29 cells stably suppressing GCF2 expression were injected into the spleens of severe combined immunodeficient (SCID) mice. GCF2 suppression reduced the number of metastatic foci in the liver and reduced fibronectin-induced cell adhesion, migration, and invasion. Downstream from the integrin signaling pathways, GCF2 regulates RhoA interaction with the RGS domain of Leukemia associated RhoGEF (LARG). Altogether, our results suggest that GCF2 plays an important role in colorectal cancer metastasis by regulating RhoA-induced cell adhesion, migration, and invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / physiology
  • Cell Movement / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • HT29 Cells
  • Humans
  • Integrins / genetics*
  • Integrins / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary*
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Rho Guanine Nucleotide Exchange Factors
  • Signal Transduction / genetics
  • rhoA GTP-Binding Protein / genetics*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • ARHGEF12 protein, human
  • Fibronectins
  • Guanine Nucleotide Exchange Factors
  • Integrins
  • LRRFIP1 protein, human
  • RNA-Binding Proteins
  • Rho Guanine Nucleotide Exchange Factors
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • rhoA GTP-Binding Protein