Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src

PLoS One. 2011;6(5):e19945. doi: 10.1371/journal.pone.0019945. Epub 2011 May 27.

Abstract

Endometrial cancer is the most common gynecologic malignancy diagnosed among women in developed countries. One recent biomarker strongly associated with disease progression and survival is epithelial membrane protein-2 (EMP2), a tetraspan protein known to associate with and modify surface expression of certain integrin isoforms. In this study, we show using a xenograft model system that EMP2 expression is necessary for efficient endometrial tumor formation, and we have started to characterize the mechanism by which EMP2 contributes to this malignant phenotype. In endometrial cancer cells, the focal adhesion kinase (FAK)/Src pathway appears to regulate migration as measured through wound healing assays. Manipulation of EMP2 levels in endometrial cancer cells regulates the phosphorylation of FAK and Src, and promotes their distribution into lipid raft domains. Notably, cells with low levels of EMP2 fail to migrate and poorly form tumors in vivo. These findings reveal the pivotal role of EMP2 in endometrial cancer carcinogenesis, and suggest that the association of elevated EMP2 levels with endometrial cancer prognosis may be causally linked to its effect on integrin-mediated signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Endometrial Neoplasms / enzymology*
  • Endometrial Neoplasms / pathology*
  • Enzyme Activation
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Membrane Microdomains / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Phosphorylation
  • Precancerous Conditions / enzymology*
  • Precancerous Conditions / pathology*
  • Protein Binding
  • Protein Transport
  • Signal Transduction
  • Tumor Burden
  • Wound Healing
  • src-Family Kinases / metabolism*

Substances

  • EMP2 protein, human
  • Membrane Glycoproteins
  • Focal Adhesion Protein-Tyrosine Kinases
  • src-Family Kinases