Expression and roles of Wilms' tumor 1-associating protein in glioblastoma

Cancer Sci. 2012 Dec;103(12):2102-9. doi: 10.1111/cas.12022. Epub 2012 Oct 22.

Abstract

Glioblastoma is a diffusely growing malignant brain tumor and among the most aggressive of all tumors. Wilms' tumor 1-associating protein (WTAP) is a nuclear protein that has been associated with regulation of proliferation and apoptosis. Although its dynamic expression and physiological functions in vascular cells have been reported, those in other cells are largely unknown. Here, we show for the first time that WTAP is overexpressed in glioblastoma. Moreover we found that WTAP regulates migration and invasion of glioblatoma cells. Specific knockdown by siRNA or overexpression by cDNA regulated migration and invasion of cancer cells. In xenograft study, WTAP overexpression made cancer cells more tumorigenic. In the investigation for its underlying mechanism, we found that the activity of epidermal growth factor receptor can be regulated by WTAP. These results reveal a novel function of WTAP and suggest its clinical application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Movement
  • DNA, Complementary / genetics
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Humans
  • Mice
  • Neoplasm Transplantation
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • RNA Splicing Factors
  • RNA, Small Interfering / metabolism
  • Transplantation, Heterologous

Substances

  • Cell Cycle Proteins
  • DNA, Complementary
  • Nuclear Proteins
  • RNA Splicing Factors
  • RNA, Small Interfering
  • WTAP protein, human
  • ErbB Receptors