ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 25956Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2016. Vol. 6, 25956
Cancer and Oncology Neurology
IdentifiersURN: urn:nbn:se:uu:diva-308256DOI: 10.1038/srep25956ISI: 000380208400001PubMedID: 27456282OAI: oai:DiVA.org:uu-308256DiVA: diva2:1049440
FunderNIH (National Institute of Health), U01 CA141502 U54 CA143798 U54CA163167 RO1 CA94842 5 P30 CA008748-44Swedish Research CouncilSwedish Childhood Cancer FoundationSwedish Cancer Society