Intrinsic interferon signaling regulates the cell death and mesenchymal phenotype of glioblastoma stem cells

Sabbir Khan, Rajasekaran Mahalingam, Shayak Sen, Emmanuel Martinez-Ledesma, Arshad Khan, Kaitlin Gandy, Frederick F. Lang, Erik P. Sulman, Kristin D. Alfaro-Munoz, Nazanin K. Majd, Veerakumar Balasubramaniyan, John F. de Groot

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number5284
JournalCancers
Volume13
Issue number21
DOIs
StatePublished - Nov 1 2021

Keywords

  • Apoptosis
  • Cell proliferation
  • Glioblastoma
  • Glioma stem-like cell
  • Interferon signaling
  • STAT1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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