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BMP signaling mediates glioma stem cell quiescence and confers treatment resistance in glioblastoma.

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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Sachdeva R,Wu M,Johnson K,Kim H,Celebre A,Shahzad U,Graham MS,Kessler JA,Chuang JH,Karamchandani J,Bredel M,Verhaak R,Das S

doi

10.1038/s41598-019-51270-1

subject

Has Abstract

pub_date

2019-10-10 00:00:00

pages

14569

issue

1

issn

2045-2322

pii

10.1038/s41598-019-51270-1

journal_volume

9

pub_type

杂志文章

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