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Cancer clocks in tumourigenesis : the p53 pathway and beyond
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Stephenson, Ewan Michael, Usselmann, Laura Emma Jane, Tergaonkar, Vinay, Virshup, David and Dallmann, Robert (2021) Cancer clocks in tumourigenesis : the p53 pathway and beyond. Endocrine-Related Cancer, 28 (4). R95-R110. doi:10.1530/ERC-20-0475
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WRAP-cancer-clocks-tumourigenesis-p53-pathway-beyond-Dallmann-2021.pdf - Accepted Version - Requires a PDF viewer. Download (1480Kb) | Preview |
Official URL: http://dx.doi.org/10.1530/ERC-20-0475
Abstract
Circadian rhythms regulate a vast array of physiological and cellular processes, as well as the hormonal milieu, to keep our cells synchronised to the light-dark cycle. Epidemiologic studies have implicated circadian disruption in the development of breast and other cancers, and numerous clock genes are dysregulated in human tumours. Here we review the evidence that circadian rhythms, when altered at the molecular level, influence cancer growth. We also note some common pitfalls in circadian-cancer research and how they might be avoided to maximise comparable results and minimise misleading data. Studies of circadian gene mutant mice, and human cancer models in vitro and in vivo, demonstrate that clock genes can impact tumourigenesis. Clock genes influence important cancer related pathways, ranging from p53-mediated apoptosis to cell cycle progression. Confusingly, clock dysfunction can be both pro- or anti- tumourigenic in a model and cell type specific manner. Due to this duality, there is no canonical mechanism for clock interaction with tumourigenic pathways. To understand the role of the circadian clock in patients’ tumours requires analysis of the molecular clock status compared to healthy tissue. Novel mathematical approaches are under development, but this remains largely aspirational, and is hampered by a lack of temporal information in publicly available datasets. Current evidence broadly supports the notion that the circadian clock is important for cancer biology. More work is necessary to develop an overarching model of this connection. Future studies would do well to analyse the clock network in addition to alterations in single clock genes.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Cancer, Tumors, p53 antioncogene, Circadian rhythms | ||||||||||||||||||||||||||||||
| Journal or Publication Title: | Endocrine-Related Cancer | ||||||||||||||||||||||||||||||
| Publisher: | BioScientifica | ||||||||||||||||||||||||||||||
| ISSN: | 1351-0088 | ||||||||||||||||||||||||||||||
| Official Date: | 1 February 2021 | ||||||||||||||||||||||||||||||
| Dates: |
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| Volume: | 28 | ||||||||||||||||||||||||||||||
| Number: | 4 | ||||||||||||||||||||||||||||||
| Page Range: | R95-R110 | ||||||||||||||||||||||||||||||
| DOI: | 10.1530/ERC-20-0475 | ||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||||||||
| Publisher Statement: | Disclaimer: this is not the definitive Version of Record of this article. This manuscript has been accepted for publication in Endocrine-Related Cancer, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. | ||||||||||||||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||||||||||||||||||||||
| Copyright Holders: | © 2021 Society for Endocrinology 2021 | ||||||||||||||||||||||||||||||
| Description: | Free access |
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