SLUG and Truncated TAL1 Reduce Glioblastoma Stem Cell Growth Downstream of Notch1 and Define Distinct Vascular Subpopulations in Glioblastoma Multiforme

Glioblastomas (GBM) are high-grade brain tumors, containing cells with distinct phenotypes and tumorigenic potentials, notably aggressive and treatment-resistant multipotent glioblastoma stem cells (GSC). The molecular mechanisms controlling GSC plasticity and growth have only partly been elucidated...

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Autores principales:	Sophie Guelfi, Béatrice Orsetti, Virginie Deleuze, Valérie Rigau, Luc Bauchet, Hugues Duffau, Bernard Rothhut, Jean-Philippe Hugnot
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	glioblastoma multiforme (GBM) glioblastoma stem cells (GSC) GSC growth GBM microenvironment notch signaling TGF-β signaling Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/b81289e9aded462483d1b85239e24bd9
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spelling	oai:doaj.org-article:b81289e9aded462483d1b85239e24bd92021-11-11T15:29:49ZSLUG and Truncated TAL1 Reduce Glioblastoma Stem Cell Growth Downstream of Notch1 and Define Distinct Vascular Subpopulations in Glioblastoma Multiforme10.3390/cancers132153932072-6694https://doaj.org/article/b81289e9aded462483d1b85239e24bd92021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5393https://doaj.org/toc/2072-6694Glioblastomas (GBM) are high-grade brain tumors, containing cells with distinct phenotypes and tumorigenic potentials, notably aggressive and treatment-resistant multipotent glioblastoma stem cells (GSC). The molecular mechanisms controlling GSC plasticity and growth have only partly been elucidated. Contact with endothelial cells and the Notch1 pathway control GSC proliferation and fate. We used three GSC cultures and glioma resections to examine the expression, regulation, and role of two transcription factors, SLUG (SNAI2) and TAL1 (SCL), involved in epithelial to mesenchymal transition (EMT), hematopoiesis, vascular identity, and treatment resistance in various cancers. In vitro, SLUG and a truncated isoform of TAL1 (TAL1-PP22) were strongly upregulated upon Notch1 activation in GSC, together with LMO2, a known cofactor of TAL1, which formed a complex with truncated TAL1. SLUG was also upregulated by TGF-β1 treatment and by co-culture with endothelial cells. In patient samples, the full-length isoform TAL1-PP42 was expressed in all glioma grades. In contrast, SLUG and truncated TAL1 were preferentially overexpressed in GBMs. SLUG and TAL1 are expressed in the tumor microenvironment by perivascular and endothelial cells, respectively, and to a minor extent, by a fraction of epidermal growth factor receptor (EGFR) -amplified GBM cells. Mechanistically, both SLUG and truncated TAL1 reduced GSC growth after their respective overexpression. Collectively, this study provides new evidence for the role of SLUG and TAL1 in regulating GSC plasticity and growth.Sophie GuelfiBéatrice OrsettiVirginie DeleuzeValérie RigauLuc BauchetHugues DuffauBernard RothhutJean-Philippe HugnotMDPI AGarticleglioblastoma multiforme (GBM)glioblastoma stem cells (GSC)GSC growthGBM microenvironmentnotch signalingTGF-β signalingNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5393, p 5393 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glioblastoma multiforme (GBM) glioblastoma stem cells (GSC) GSC growth GBM microenvironment notch signaling TGF-β signaling Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	glioblastoma multiforme (GBM) glioblastoma stem cells (GSC) GSC growth GBM microenvironment notch signaling TGF-β signaling Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Sophie Guelfi Béatrice Orsetti Virginie Deleuze Valérie Rigau Luc Bauchet Hugues Duffau Bernard Rothhut Jean-Philippe Hugnot SLUG and Truncated TAL1 Reduce Glioblastoma Stem Cell Growth Downstream of Notch1 and Define Distinct Vascular Subpopulations in Glioblastoma Multiforme
description	Glioblastomas (GBM) are high-grade brain tumors, containing cells with distinct phenotypes and tumorigenic potentials, notably aggressive and treatment-resistant multipotent glioblastoma stem cells (GSC). The molecular mechanisms controlling GSC plasticity and growth have only partly been elucidated. Contact with endothelial cells and the Notch1 pathway control GSC proliferation and fate. We used three GSC cultures and glioma resections to examine the expression, regulation, and role of two transcription factors, SLUG (SNAI2) and TAL1 (SCL), involved in epithelial to mesenchymal transition (EMT), hematopoiesis, vascular identity, and treatment resistance in various cancers. In vitro, SLUG and a truncated isoform of TAL1 (TAL1-PP22) were strongly upregulated upon Notch1 activation in GSC, together with LMO2, a known cofactor of TAL1, which formed a complex with truncated TAL1. SLUG was also upregulated by TGF-β1 treatment and by co-culture with endothelial cells. In patient samples, the full-length isoform TAL1-PP42 was expressed in all glioma grades. In contrast, SLUG and truncated TAL1 were preferentially overexpressed in GBMs. SLUG and TAL1 are expressed in the tumor microenvironment by perivascular and endothelial cells, respectively, and to a minor extent, by a fraction of epidermal growth factor receptor (EGFR) -amplified GBM cells. Mechanistically, both SLUG and truncated TAL1 reduced GSC growth after their respective overexpression. Collectively, this study provides new evidence for the role of SLUG and TAL1 in regulating GSC plasticity and growth.
format	article
author	Sophie Guelfi Béatrice Orsetti Virginie Deleuze Valérie Rigau Luc Bauchet Hugues Duffau Bernard Rothhut Jean-Philippe Hugnot
author_facet	Sophie Guelfi Béatrice Orsetti Virginie Deleuze Valérie Rigau Luc Bauchet Hugues Duffau Bernard Rothhut Jean-Philippe Hugnot
author_sort	Sophie Guelfi
title	SLUG and Truncated TAL1 Reduce Glioblastoma Stem Cell Growth Downstream of Notch1 and Define Distinct Vascular Subpopulations in Glioblastoma Multiforme
title_short	SLUG and Truncated TAL1 Reduce Glioblastoma Stem Cell Growth Downstream of Notch1 and Define Distinct Vascular Subpopulations in Glioblastoma Multiforme
title_full	SLUG and Truncated TAL1 Reduce Glioblastoma Stem Cell Growth Downstream of Notch1 and Define Distinct Vascular Subpopulations in Glioblastoma Multiforme
title_fullStr	SLUG and Truncated TAL1 Reduce Glioblastoma Stem Cell Growth Downstream of Notch1 and Define Distinct Vascular Subpopulations in Glioblastoma Multiforme
title_full_unstemmed	SLUG and Truncated TAL1 Reduce Glioblastoma Stem Cell Growth Downstream of Notch1 and Define Distinct Vascular Subpopulations in Glioblastoma Multiforme
title_sort	slug and truncated tal1 reduce glioblastoma stem cell growth downstream of notch1 and define distinct vascular subpopulations in glioblastoma multiforme
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b81289e9aded462483d1b85239e24bd9
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SLUG and Truncated TAL1 Reduce Glioblastoma Stem Cell Growth Downstream of Notch1 and Define Distinct Vascular Subpopulations in Glioblastoma Multiforme

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