BMP signaling mediates glioma stem cell quiescence and confers treatment resistance in glioblastoma.
Document Type
Article
Publication Date
10-10-2019
Keywords
JGM
JAX Source
Sci Rep 2019 Oct 10; 9(1):14569
Volume
9
Issue
1
First Page
14569
Last Page
14569
ISSN
2045-2322
PMID
31602000
DOI
https://doi.org/10.1038/s41598-019-51270-1
Abstract
Despite advances in therapy, glioblastoma remains an incurable disease with a dismal prognosis. Recent studies have implicated cancer stem cells within glioblastoma (glioma stem cells, GSCs) as mediators of therapeutic resistance and tumor progression. In this study, we investigated the role of the transforming growth factor-β (TGF-β) superfamily, which has been found to play an integral role in the maintenance of stem cell homeostasis within multiple stem cell systems, as a mediator of stem-like cells in glioblastoma. We find that BMP and TGF-β signaling define divergent molecular and functional identities in glioblastoma, and mark relatively quiescent and proliferative GSCs, respectively. Treatment of GSCs with BMP inhibits cell proliferation, but does not abrogate their stem-ness, as measured by self-renewal and tumorigencity. Further, BMP pathway activation confers relative resistance to radiation and temozolomide chemotherapy. Our findings define a quiescent cancer stem cell population in glioblastoma that may be a cellular reservoir for tumor recurrence following cytotoxic therapy.
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This open access article is licensed under a Creative Commons Attribution 4.0 International License.