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 beta-catenin/TCF-induced transcription. Levels of reactive oxygen species decreased in suspension and knockdown of HIF-1 alpha enhanced cell death following detachment. By promoting the adaptation to non-adherent conditions, mechanisms driven by HIF-1 alpha may considerably contribute to the biology and aggressiveness of glioblastoma. (C) 2019 Elsevier Inc. All rights reserved.