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Targeting LGR5 in Colorectal Cancer: Therapeutic gold or too plastic?

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Targeting LGR5 in Colorectal Cancer : Therapeutic gold or too plastic? / Morgan, R. G.; Mortensson, E.; Williams, A. C.

In: British Journal of Cancer, Vol. 118, No. 11, 30.05.2018, p. 1410-1418.

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Morgan, R. G. ; Mortensson, E. ; Williams, A. C. / Targeting LGR5 in Colorectal Cancer : Therapeutic gold or too plastic?. In: British Journal of Cancer. 2018 ; Vol. 118, No. 11. pp. 1410-1418.

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@article{571c35e575ad4a3c989badcdfcdc1747,
title = "Targeting LGR5 in Colorectal Cancer: Therapeutic gold or too plastic?",
abstract = "Leucine-rich repeat-containing G-protein coupled receptor (LGR5 or GPR49) potentiates canonical Wnt/β-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-organising crypt/villus structures in vitro termed organoids or 'mini-guts', which accurately model the parent tissue. The well characterised deregulation of Wnt/β-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.",
keywords = "LGR5, colorectal cancer, stem cells, oncogene, tumour suppressor, plasticity",
author = "Morgan, {R. G.} and E. Mortensson and Williams, {A. C.}",
year = "2018",
month = "5",
day = "30",
doi = "10.1038/s41416-018-0118-6",
language = "English",
volume = "118",
pages = "1410--1418",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Springer Nature",
number = "11",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Targeting LGR5 in Colorectal Cancer

T2 - Therapeutic gold or too plastic?

AU - Morgan, R. G.

AU - Mortensson, E.

AU - Williams, A. C.

PY - 2018/5/30

Y1 - 2018/5/30

N2 - Leucine-rich repeat-containing G-protein coupled receptor (LGR5 or GPR49) potentiates canonical Wnt/β-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-organising crypt/villus structures in vitro termed organoids or 'mini-guts', which accurately model the parent tissue. The well characterised deregulation of Wnt/β-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.

AB - Leucine-rich repeat-containing G-protein coupled receptor (LGR5 or GPR49) potentiates canonical Wnt/β-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-organising crypt/villus structures in vitro termed organoids or 'mini-guts', which accurately model the parent tissue. The well characterised deregulation of Wnt/β-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.

KW - LGR5

KW - colorectal cancer

KW - stem cells

KW - oncogene

KW - tumour suppressor

KW - plasticity

UR - http://www.scopus.com/inward/record.url?scp=85047666051&partnerID=8YFLogxK

U2 - 10.1038/s41416-018-0118-6

DO - 10.1038/s41416-018-0118-6

M3 - Article

VL - 118

SP - 1410

EP - 1418

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 11

ER -