TY - JOUR
T1 - Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells
AU - Khan, Sabbir
AU - Mahalingam, Rajasekaran
AU - Sen, Shayak
AU - Martinez-Ledesma, Emmanuel
AU - Khan, Arshad
AU - Gandy, Kaitlin
AU - Lang, Frederick F
AU - Sulman, Erik P
AU - Alfaro-Munoz, Kristin D
AU - Majd, Nazanin K
AU - Balasubramaniyan, Veerakumar
AU - de Groot, John F
PY - 2021/10/21
Y1 - 2021/10/21
N2 - Interferon (IFN) signaling contributes to stemness, cell proliferation, cell death, and cytokine signaling in cancer and immune cells; however, the role of IFN signaling in glioblastoma (GBM) and GBM stem-like cells (GSCs) is unclear. Here, we investigated the role of cancer-cell-intrinsic IFN signaling in tumorigenesis in GBM. We report here that GSCs and GBM tumors exhibited differential cell-intrinsic type I and type II IFN signaling, and high IFN/STAT1 signaling was associated with mesenchymal phenotype and poor survival outcomes. In addition, chronic inhibition of IFN/STAT1 signaling decreased cell proliferation and mesenchymal signatures in GSCs with intrinsically high IFN/STAT1 signaling. IFN-β exposure induced apoptosis in GSCs with intrinsically high IFN/STAT1 signaling, and this effect was abolished by the pharmacological inhibitor ruxolitinib and STAT1 knockdown. We provide evidence for targeting IFN signaling in a specific sub-group of GBM patients. IFN-β may be a promising candidate for adjuvant GBM therapy.
AB - Interferon (IFN) signaling contributes to stemness, cell proliferation, cell death, and cytokine signaling in cancer and immune cells; however, the role of IFN signaling in glioblastoma (GBM) and GBM stem-like cells (GSCs) is unclear. Here, we investigated the role of cancer-cell-intrinsic IFN signaling in tumorigenesis in GBM. We report here that GSCs and GBM tumors exhibited differential cell-intrinsic type I and type II IFN signaling, and high IFN/STAT1 signaling was associated with mesenchymal phenotype and poor survival outcomes. In addition, chronic inhibition of IFN/STAT1 signaling decreased cell proliferation and mesenchymal signatures in GSCs with intrinsically high IFN/STAT1 signaling. IFN-β exposure induced apoptosis in GSCs with intrinsically high IFN/STAT1 signaling, and this effect was abolished by the pharmacological inhibitor ruxolitinib and STAT1 knockdown. We provide evidence for targeting IFN signaling in a specific sub-group of GBM patients. IFN-β may be a promising candidate for adjuvant GBM therapy.
U2 - 10.3390/cancers13215284
DO - 10.3390/cancers13215284
M3 - Article
C2 - 34771447
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 21
ER -