FOXC2 promotes vasculogenic mimicry and resistance to anti-angiogenic therapy.

Autor:	Cannell IG; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA. Electronic address: Ian.Cannell@cruk.cam.ac.uk., Sawicka K; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA., Pearsall I; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA., Wild SA; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK., Deighton L; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK., Pearsall SM; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; Cancer Research UK Cancer Biomarker Centre, Manchester M20 4BX, UK; CRUK Manchester Institute, Manchester M20 4BX, UK., Lerda G; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK., Joud F; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK., Khan S; New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA., Bruna A; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; Preclinical Modelling of Paediatric Cancer Evolution Team, The Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5N, UK., Simpson KL; Cancer Research UK Cancer Biomarker Centre, Manchester M20 4BX, UK; CRUK Manchester Institute, Manchester M20 4BX, UK., Mulvey CM; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK., Nugent F; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK., Qosaj F; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK., Bressan D; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK., Dive C; Cancer Research UK Cancer Biomarker Centre, Manchester M20 4BX, UK; CRUK Manchester Institute, Manchester M20 4BX, UK., Caldas C; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; Department of Oncology and Breast Cancer Programme, CRUK Cambridge Centre, Cambridge University Hospitals NHS and University of Cambridge, Cambridge CB2 2QQ, UK., Hannon GJ; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA. Electronic address: Greg.Hannon@cruk.cam.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Aug 29; Vol. 42 (8), pp. 112791. Date of Electronic Publication: 2023 Jul 26.
DOI:	10.1016/j.celrep.2023.112791
Abstrakt:	Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood vessels, and their presence is generally associated with poor patient prognosis. Here we show that the transcription factor, Foxc2, promotes VM in diverse solid tumor types by driving ectopic expression of endothelial genes in tumor cells, a process that is stimulated by hypoxia. VM-proficient tumors are resistant to anti-angiogenic therapy, and suppression of Foxc2 augments response. This work establishes co-option of an embryonic endothelial transcription factor by tumor cells as a key mechanism driving VM proclivity and motivates the search for VM-inhibitory agents that could form the basis of combination therapies with anti-angiogenics. Competing Interests: Declaration of interests The authors have filed a patent covering use of FOXC2 and FOXC2-regulated gene sets as diagnostics and as a route toward development of VM inhibitors. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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