An ILK/STAT3 pathway controls glioblastoma stem cell plasticity.

Autor:	Loftus AEP; Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK. Electronic address: a.loftus@ed.ac.uk., Romano MS; Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK., Phuong AN; Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK., McKinnel BJ; Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK., Muir MT; Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK., Furqan M; Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK., Dawson JC; Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK., Avalle L; Department of Molecular Biotechnology and Health Science, University of Torino, Via Nizza 52, 10126 Torino, Italy., Douglas AT; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK., Mort RL; Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YG, UK., Byron A; Division of Molecular and Cellular Function, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK., Carragher NO; Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK., Pollard SM; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK., Brunton VG; Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK., Frame MC; Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK. Electronic address: m.frame@ed.ac.uk.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Sep 20. Date of Electronic Publication: 2024 Sep 20.
DOI:	10.1016/j.devcel.2024.09.003
Abstrakt:	Glioblastoma (GBM) is driven by malignant neural stem-like cells that display extensive heterogeneity and phenotypic plasticity, which drive tumor progression and therapeutic resistance. Here, we show that the extracellular matrix-cell adhesion protein integrin-linked kinase (ILK) stimulates phenotypic plasticity and mesenchymal-like, invasive behavior in a murine GBM stem cell model. ILK is required for the interconversion of GBM stem cells between malignancy-associated glial-like states, and its loss produces cells that are unresponsive to multiple cell state transition cues. We further show that an ILK/STAT3 signaling pathway controls the plasticity that enables transition of GBM stem cells to an astrocyte-like state in vitro and in vivo. Finally, we find that ILK expression correlates with expression of STAT3-regulated proteins and protein signatures describing astrocyte-like and mesenchymal states in patient tumors. This work identifies ILK as a pivotal regulator of multiple malignancy-associated GBM phenotypes, including phenotypic plasticity and mesenchymal state. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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