Subversion of niche-signalling pathways in colorectal cancer: what makes and breaks the intestinal stem cell

Sphyris, N., Hodder, M. C. and Sansom, O. J. (2021) Subversion of niche-signalling pathways in colorectal cancer: what makes and breaks the intestinal stem cell. Cancers, 13(5), 1000. (doi: 10.3390/cancers13051000) (PMID:33673710) (PMCID:PMC7957493)

[img] Text
227364.pdf - Published Version
Available under License Creative Commons Attribution.

2MB

Abstract

The intestinal epithelium fulfils pleiotropic functions in nutrient uptake, waste elimination, and immune surveillance while also forming a barrier against luminal toxins and gut-resident microbiota. Incessantly barraged by extraneous stresses, the intestine must continuously replenish its epithelial lining and regenerate the full gamut of specialized cell types that underpin its functions. Homeostatic remodelling is orchestrated by the intestinal stem cell (ISC) niche: a convergence of epithelial- and stromal-derived cues, which maintains ISCs in a multipotent state. Following demise of homeostatic ISCs post injury, plasticity is pervasive among multiple populations of reserve stem-like cells, lineage-committed progenitors, and/or fully differentiated cell types, all of which can contribute to regeneration and repair. Failure to restore the epithelial barrier risks seepage of toxic luminal contents, resulting in inflammation and likely predisposing to tumour formation. Here, we explore how homeostatic niche-signalling pathways are subverted in tumorigenesis, enabling ISCs to gain autonomy from niche restraints (“ISC emancipation”) and transform into cancer stem cells capable of driving tumour initiation, progression, and therapy resistance. We further consider the implications of the pervasive plasticity of the intestinal epithelium for the trajectory of colorectal cancer, the emergence of distinct molecular subtypes, the propensity to metastasize, and the development of effective therapeutic strategies.

Item Type:Articles
Additional Information:N.S., M.C.H. and O.J.S. are supported by Cancer Research UK (A21139, A17196).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sansom, Professor Owen and Hodder, Michael
Authors: Sphyris, N., Hodder, M. C., and Sansom, O. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cancers
Publisher:MDPI
ISSN:2072-6694
ISSN (Online):2072-6694
Published Online:27 February 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Cancers 13(5): 1000
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record