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Sci Rep. 2016 Jul 26;6:25956. doi: 10.1038/srep25956.

ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells.

Author information

1
Cancer Biology and Genetics Program, New York, NY 10021, USA.
2
Brain Tumor Center, New York, NY 10021, USA.
3
Human Biology Division, Solid Tumor and Translational Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
4
Neurosurgery and Alvord Brain Tumor Center, University of Washington, Seattle, WA 98104, USA.
5
Translational Cancer Research, Department of Laboratory Medicine, Lund University, SE-22363 Lund, Sweden.
6
Centro San Giovanni di Dio - Fatebenefratelli, IRCCS, 25123 Bs, Italy.
7
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
8
Department of Biostatistics, Harvard School of Public Health, Boston, MA 02215, USA.
9
HTS Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
10
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden.

Abstract

Glioma cells with stem cell traits are thought to be responsible for tumor maintenance and therapeutic failure. Such cells can be enriched based on their inherent drug efflux capability mediated by the ABC transporter ABCG2 using the side population assay, and their characteristics include increased self-renewal, high stem cell marker expression and high tumorigenic capacity in vivo. Here, we show that ABCG2 can actively drive expression of stem cell markers and self-renewal in glioma cells. Stem cell markers and self-renewal was enriched in cells with high ABCG2 activity, and could be specifically inhibited by pharmacological and genetic ABCG2 inhibition. Importantly, despite regulating these key characteristics of stem-like tumor cells, ABCG2 activity did not affect radiation resistance or tumorigenicity in vivo. ABCG2 effects were Notch-independent and mediated by diverse mechanisms including the transcription factor Mef. Our data demonstrate that characteristics of tumor stem cells are separable, and highlight ABCG2 as a potential driver of glioma stemness.

PMID:
27456282
PMCID:
PMC4960591
DOI:
10.1038/srep25956
[Indexed for MEDLINE]
Free PMC Article

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