AI Article Synopsis
- Stimulation of CD95/Fas promotes the growth and maintenance of cancer stem cells (CSCs) by activating STAT1 and its associated genes.
- In cancer cell lines and patient samples, STAT1 levels are higher in CSCs, and its activation is linked to the secretion of type I interferons (IFNs) which enhance CSC properties.
- Disabling STAT1 significantly decreases the ability of CD95L or type I IFN to boost CSC characteristics, establishing STAT1 as a crucial factor in the process.
Article Abstract
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 STAT1-regulated 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-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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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474321 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2017.02.037 | DOI Listing |
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