期刊
CELL REPORTS
卷 18, 期 10, 页码 2373-2386出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.02.037
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资金
- DOD postdoctoral fellowships [W81XWH-13-1-0301, R00CA160638, ACS127951-RSG-15-025-01-CS]
- Northwestern Memorial Foundation-Lynn Sage Cancer Research Foundation [R01CA149356, R35CA197450]
Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95(high)-expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus- activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers. Consequently, we identified type I IFNs as drivers of cancer stemness. Knockdown or knockout of STAT1 resulted in a strongly reduced ability of CD95L or type I IFN to increase cancer stemness. This identifies STAT1 as a key regulator of the CSC-inducing activity of CD95.
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