期刊
CELL REPORTS
卷 27, 期 3, 页码 971-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.03.047
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资金
- SU2C Canada Cancer Stem Cell Dream Team - Government of Canada through Genome Canada [SU2C-AACR-DT-19-15]
- Canadian Institutes of Health Research
- Government of Ontario
- Terry Fox Research Institute
- Canadian Institutes for Health Research
- Hospital for Sick Children Foundation
- Jessica's Footprint Foundation
- Hopeful Minds Foundation
- Bresler family
- B.R.A.I.N. Child
- MD Anderson Cancer Center Support Grant [P30 CA016672]
- Cancer Prevention Research Institute of Texas (CPRIT) [RR160032]
Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry ofGBMstemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Additionally, we reveal mechanisms of temozolomide resistance that could lead to combination strategies. By reaching beyond static genome analysis of bulk tumors, with a genome-wide functional approach, we reveal genetic dependencies within a broad range of biological processes to provide increased understanding of GBM growth and treatment resistance.
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