Loss of cell-matrix contact increases hypoxia-inducible factor-dependent transcriptional activity in glioma cells

Biochem Biophys Res Commun. 2019 Jul 12;515(1):77-84. doi: 10.1016/j.bbrc.2019.05.115. Epub 2019 May 23.

Abstract

In a variety of malignomas, the acquisition of a mesenchymal phenotype has been linked with anchorage-independent growth and invasiveness. To some extent, glioma cells are able to survive a loss of cell-matrix contact. We here describe that non-adherent culture of glioma cells was accompanied by an increase in hypoxia-inducible factor (HIF)-dependent, but not β-catenin/TCF-induced transcription. Levels of reactive oxygen species decreased in suspension and knockdown of HIF-1α enhanced cell death following detachment. By promoting the adaptation to non-adherent conditions, mechanisms driven by HIF-1α may considerably contribute to the biology and aggressiveness of glioblastoma.

Keywords: Anoikis; Epithelial-mesenchymal transition; Glioblastoma; Hypoxia-inducible factor; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anoikis / genetics
  • Cell Adhesion / genetics
  • Cell Hypoxia
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • RNA Interference
  • Reactive Oxygen Species / metabolism*

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Reactive Oxygen Species