Targeting LGR5 in colorectal cancer: therapeutic gold or too plastic?

Morgan, R G, Mortensson, E and Williams, A C (2018) Targeting LGR5 in colorectal cancer: therapeutic gold or too plastic? British Journal of Cancer, 118. pp. 1410-1418. ISSN 0007-0920

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Abstract

Leucine-rich repeat-containing G-protein coupled receptor (LGR5 or GPR49) potentiates canonical Wnt/-catenin signalling and is a marker of normal stem cells in several tissues, including the intestine. Consistent with stem cell potential, single isolated LGR5+ cells from the gut generate self-organizing crypt/villus structures in vitro termed organoids or ‘mini-guts’, which accurately model the parent tissue. The well characterised deregulation of Wnt/-catenin signalling that occurs during the adenoma-carcinoma sequence in colorectal cancer (CRC) renders LGR5 an interesting therapeutic target. Furthermore, recent studies demonstrating that CRC tumours contain LGR5+ subsets and retain a degree of normal tissue architecture has heightened translational interest. Such reports fuel hope that specific subpopulations or molecules within a tumour may be therapeutically targeted to prevent relapse and induce long-term remissions. Despite these observations, many studies within this field have produced conflicting and confusing results with no clear consensus on the therapeutic value of LGR5. This review will recap the various oncogenic and tumour suppressive roles that have been described for the LGR5 molecule in CRC. It will further highlight recent studies indicating the plasticity or redundancy of LGR5+ cells in intestinal cancer progression and assess the overall merit of therapeutically targeting LGR5 in CRC.

Item Type: Article
Keywords: LGR5 Colorectal Cancer Stem Cells Oncogene Tumour Suppressor Plasticity
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Rhys Morgan
Date Deposited: 10 May 2018 15:22
Last Modified: 02 Jul 2019 15:15
URI: http://sro.sussex.ac.uk/id/eprint/75757

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