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TMEFF2 is a PDGF-AA binding protein with methylation-associated gene silencing in multiple cancer types including

Kui Lin1, James R Taylor, Thomas D Wu

  • 1Genentech, South San Francisco, California, United States of America. klin@gene.com

Plos One
|May 12, 2011
PubMed
Abstract

Insights

The TMEFF2 protein regulates PDGF signaling and is downregulated in human cancers due to hypermethylation. This suggests TMEFF2 plays a role in cancer development.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • TMEFF2 (a protein with EGF-like and follistatin modules) has an unclear role in human cancers.
  • Conflicting reports exist regarding TMEFF2's association with cancer.
  • This study investigates TMEFF2's function and its role in cancer etiology.

Purpose of the Study:

  • To elucidate the biological function of the TMEFF2 protein.
  • To investigate the interaction of TMEFF2 with PDGF-AA.
  • To determine the role of TMEFF2 in human cancers, particularly brain tumors.

Main Methods:

  • Investigated the interaction between the extracellular domain of TMEFF2 and PDGF-AA.
  • Assessed the effect of TMEFF2 on PDGF-AA-stimulated fibroblast proliferation.
  • Analyzed TMEFF2 expression, hypermethylation, and correlation with PDGF-AA in various human cancers, including gliomas.

Main Results:

  • The extracellular domain of TMEFF2 interacts with PDGF-AA, mediated by its follistatin modules.
  • TMEFF2 inhibits PDGF-AA-stimulated fibroblast proliferation.
  • TMEFF2 is downregulated and hypermethylated in human brain cancers and other tumor types, negatively correlating with PDGF-AA expression.

Conclusions:

  • TMEFF2 regulates PDGF signaling, indicating a functional role in cell proliferation.
  • TMEFF2 is frequently hypermethylated and downregulated in multiple human cancers, including glioma.
  • These findings suggest TMEFF2 is important in the development of human cancers.

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