The small GTPase Rac1 is involved in the maintenance of stemness and malignancies in glioma stem-like cells

FEBS Lett. 2011 Jul 21;585(14):2331-8. doi: 10.1016/j.febslet.2011.05.070. Epub 2011 Jun 23.

Abstract

A subpopulation of cancer cells with stem cell properties is responsible for tumor formation, maintenance, and malignant progression; however, the molecular mechanisms underlying the maintenance of cancer stem-like cell properties have remained unclear. Here, we show that the Rho family GTPase Rac1 is involved in the glioma stem-like cell (GSLC) maintenance and tumorigenicity in human glioma. The Rac1-Pak signaling was markedly activated in GSLCs. Knockdown of Rac1 caused reduction of expression of GSLC markers, self-renewal-related proteins and neurosphere formation. Moreover, down-regulation of Rac1 suppressed the migration, invasion, and malignant transformation in GSLCs. Furthermore, inhibition of Rac1 enhanced radiation sensitivity of GSLCs. These results indicate that the small GTPase Rac1 is involved in the maintenance of stemness and malignancies in GSLCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction / physiology
  • p21-Activated Kinases / metabolism
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism*

Substances

  • RNA, Small Interfering
  • p21-Activated Kinases
  • rac1 GTP-Binding Protein