Pan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signature.

Autor:	Lombardi O; NDM Research Building, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, UK., Li R; NDM Research Building, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, UK., Halim S; NDM Research Building, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, UK., Choudhry H; Department of Biochemistry, Faculty of Science, Center of Innovation in Personalized Medicine, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia., Ratcliffe PJ; Ludwig Institute for Cancer Research, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, UK; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Mole DR; NDM Research Building, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, UK. Electronic address: david.mole@ndm.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Nov 15; Vol. 41 (7), pp. 111652.
DOI:	10.1016/j.celrep.2022.111652
Abstrakt:	Activation of cellular hypoxia pathways, orchestrated by HIF (hypoxia-inducible factor) transcription factors, is a common feature of multiple tumor types, resulting from microenvironment factors and oncogenic mutation. Although they help drive many of the "hallmarks" of cancer and are associated with poor outcome and resistance to therapy, the transcriptional targets of HIF vary considerably depending on the cell type. By integrating 72 genome-wide assays of HIF binding and transcriptional regulation from multiple cancer types, we define a consensus set of 48 HIF target genes that is highly conserved across cancer types and cell lineages. These genes provide an effective marker of HIF activation in bulk and single-cell transcriptomic analyses across a wide range of cancer types and in malignant and stromal cell types. This allows the tissue-orchestrated responses to the hypoxic tumor microenvironment and to oncogenic HIF activation to be deconvoluted at the tumor and single-cell level. Competing Interests: Declaration of interests P.J.R. is a scientific co-founder of ReOx Ltd., a company developing inhibitors of the HIF hydroxylase enzymes. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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