Presenting Author:

Abdul Qadir Syed, Ph.D.

Principal Investigator:

Marcus Peter, Ph.D.

Department:

Medicine

Keywords:

STAT1, Fas, cancer stem cells, type I interferons, breast cancer, head and neck cancer

Location:

Third Floor, Feinberg Pavilion, Northwestern Memorial Hospital

B50 - Basic Science Women's Health Research

CD95/Fas Increases Cancer Stemness by Inducing a STAT1 Dependent Type I Interferon Response

Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We have identified STAT1 as a regulator of this activity. Stimulation of CD95 causes activation of STAT1 and induction of STAT1 regulated genes and this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and glioblastoma neurospheres sorted for high CD95 expression. CD95 stimulation of cancer cells induced secretion of Type I interferons (IFNs) that bind to Type I IFN receptors, resulting in activation of JAK 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 5 primary human cancers. Consequently, we identified Type I IFNs as drivers of cancer stemness. Knockdown or knock-out 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. *Paper accepted in Cell Reports and currently in press