Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells

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 signa...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	glioblastoma interferon signaling apoptosis glioma stem-like cell STAT1 cell proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9a0400ac6bca4615aa0d2f214f8962d5
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spelling	oai:doaj.org-article:9a0400ac6bca4615aa0d2f214f8962d52021-11-11T15:27:06ZIntrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells10.3390/cancers132152842072-6694https://doaj.org/article/9a0400ac6bca4615aa0d2f214f8962d52021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5284https://doaj.org/toc/2072-6694Interferon (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.Sabbir KhanRajasekaran MahalingamShayak SenEmmanuel Martinez-LedesmaArshad KhanKaitlin GandyFrederick F. LangErik P. SulmanKristin D. Alfaro-MunozNazanin K. MajdVeerakumar BalasubramaniyanJohn F. de GrootMDPI AGarticleglioblastomainterferon signalingapoptosisglioma stem-like cellSTAT1cell proliferationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5284, p 5284 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glioblastoma interferon signaling apoptosis glioma stem-like cell STAT1 cell proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	glioblastoma interferon signaling apoptosis glioma stem-like cell STAT1 cell proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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 Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells
description	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.
format	article
author	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
author_facet	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
author_sort	Sabbir Khan
title	Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells
title_short	Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells
title_full	Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells
title_fullStr	Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells
title_full_unstemmed	Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells
title_sort	intrinsic interferon signaling regulates the cell death and mesenchymal phenotype of glioblastoma stem cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9a0400ac6bca4615aa0d2f214f8962d5
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Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells

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