Håkan Axelson
Research team manager
CD44 interacts with HIF-2α to modulate the hypoxic phenotype of perinecrotic and perivascular glioma cells
Author
Summary, in English
Hypoxia-inducible factors enhance glioma stemness, and glioma stem cells have an amplified hypoxic response despite residing within a perivascular niche. Still, little is known about differential HIF regulation in stem versus bulk glioma cells. We show that the intracellular domain of stem cell marker CD44 (CD44ICD) is released at hypoxia, binds HIF-2α (but not HIF-1α), enhances HIF target gene activation, and is required for hypoxia-induced stemness in glioma. In a glioma mouse model, CD44 was restricted to hypoxic and perivascular tumor regions, and in human glioma, a hypoxia signature correlated with CD44. The CD44ICD was sufficient to induce hypoxic signaling at perivascular oxygen tensions, and blocking CD44 cleavage decreased HIF-2α stabilization in CD44-expressing cells. Our data indicate that the stem cell marker CD44 modulates the hypoxic response of glioma cells and that the pseudo-hypoxic phenotype of stem-like glioma cells is achieved by stabilization of HIF-2α through interaction with CD44, independently of oxygen.
Department/s
- Division of Translational Cancer Research
- Brain Tumor Biology
- Kidney cancer research group
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2017-08
Language
English
Pages
1641-1653
Publication/Series
Cell Reports
Volume
20
Issue
7
Document type
Journal article
Publisher
Cell Press
Topic
- Cell and Molecular Biology
Status
Published
Project
- The role of FIH-1 in glioblastoma multiforme
Research group
- Brain Tumor Biology
- Kidney cancer research group
ISBN/ISSN/Other
- ISSN: 2211-1247