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

• Published in: Biochemical and biophysical research communications Vol. 515; no. 1; pp. 77 - 84
• Main Authors: Maurer, Gabriele D., Brucker, Daniel P., Steinbach, Joachim P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.07.2019
• Subjects: Anoikis; Epithelial-mesenchymal transition; Glioblastoma; Hypoxia-inducible factor; Reactive oxygen species; Hypoxia-inducible factor; Epithelial-mesenchymal transition; Anoikis; Reactive oxygen species; Glioblastoma
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.05.115

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. [Display omitted] •HIF-specific transcriptional activity increases upon loss of cell-matrix contact.•Cells surviving in suspension culture have lower levels of reactive oxygen species.•Knockdown of HIF-1α, but not HIF-2α, sensitizes LNT-229 cells to anoikis.