LGR5 is a negative regulator of tumourigenicity, antagonizes Wnt signalling and regulates cell adhesion in colorectal cancer cell lines.

<h4>Background</h4>LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5) is the most established marker for intestinal stem cells. Mouse models show that LGR5+ cells are the cells of origin of intestinal cancer, and LGR5 expression is elevated in human colorectal cancers, ho...

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Autores principales: Francesca Walker, Hui-Hua Zhang, Annalisa Odorizzi, Antony W Burgess
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Publicado: Public Library of Science (PLoS) 2011
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Acceso en línea:https://doaj.org/article/17c6b9b10c5045ddaa12ea2b61b46ec1
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spelling oai:doaj.org-article:17c6b9b10c5045ddaa12ea2b61b46ec12021-11-18T06:49:09ZLGR5 is a negative regulator of tumourigenicity, antagonizes Wnt signalling and regulates cell adhesion in colorectal cancer cell lines.1932-620310.1371/journal.pone.0022733https://doaj.org/article/17c6b9b10c5045ddaa12ea2b61b46ec12011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21829496/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5) is the most established marker for intestinal stem cells. Mouse models show that LGR5+ cells are the cells of origin of intestinal cancer, and LGR5 expression is elevated in human colorectal cancers, however very little is known about LGR5 function or its contribution to the stem cell phenotype and to colorectal cancer.<h4>Principal findings</h4>We have modulated the expression of LGR5 by RNAi (inhibitory RNAs) or overexpression in colorectal cancer cell lines. Paradoxically, ablation of LGR5 induces increased invasion and anchorage-independent growth, and enhances tumourigenicity in xenografts experiments. Conversely, overexpression of LGR5 augments cell adhesion, reduces clonogenicity and attenuates tumourigenicity. Expression profiling revealed enhanced wnt signalling and upregulation of EMT genes upon knockdown of LGR5, with opposite changes in LGR5 overexpressing cells. These findings suggest that LGR5 is important in restricting stem cells to their niche, and that loss of LGR5 concomitant with activated wnt signalling may contribute to the invasive phenotype of colorectal carcinomas.Francesca WalkerHui-Hua ZhangAnnalisa OdorizziAntony W BurgessPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22733 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Francesca Walker
Hui-Hua Zhang
Annalisa Odorizzi
Antony W Burgess
LGR5 is a negative regulator of tumourigenicity, antagonizes Wnt signalling and regulates cell adhesion in colorectal cancer cell lines.
description <h4>Background</h4>LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5) is the most established marker for intestinal stem cells. Mouse models show that LGR5+ cells are the cells of origin of intestinal cancer, and LGR5 expression is elevated in human colorectal cancers, however very little is known about LGR5 function or its contribution to the stem cell phenotype and to colorectal cancer.<h4>Principal findings</h4>We have modulated the expression of LGR5 by RNAi (inhibitory RNAs) or overexpression in colorectal cancer cell lines. Paradoxically, ablation of LGR5 induces increased invasion and anchorage-independent growth, and enhances tumourigenicity in xenografts experiments. Conversely, overexpression of LGR5 augments cell adhesion, reduces clonogenicity and attenuates tumourigenicity. Expression profiling revealed enhanced wnt signalling and upregulation of EMT genes upon knockdown of LGR5, with opposite changes in LGR5 overexpressing cells. These findings suggest that LGR5 is important in restricting stem cells to their niche, and that loss of LGR5 concomitant with activated wnt signalling may contribute to the invasive phenotype of colorectal carcinomas.
format article
author Francesca Walker
Hui-Hua Zhang
Annalisa Odorizzi
Antony W Burgess
author_facet Francesca Walker
Hui-Hua Zhang
Annalisa Odorizzi
Antony W Burgess
author_sort Francesca Walker
title LGR5 is a negative regulator of tumourigenicity, antagonizes Wnt signalling and regulates cell adhesion in colorectal cancer cell lines.
title_short LGR5 is a negative regulator of tumourigenicity, antagonizes Wnt signalling and regulates cell adhesion in colorectal cancer cell lines.
title_full LGR5 is a negative regulator of tumourigenicity, antagonizes Wnt signalling and regulates cell adhesion in colorectal cancer cell lines.
title_fullStr LGR5 is a negative regulator of tumourigenicity, antagonizes Wnt signalling and regulates cell adhesion in colorectal cancer cell lines.
title_full_unstemmed LGR5 is a negative regulator of tumourigenicity, antagonizes Wnt signalling and regulates cell adhesion in colorectal cancer cell lines.
title_sort lgr5 is a negative regulator of tumourigenicity, antagonizes wnt signalling and regulates cell adhesion in colorectal cancer cell lines.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/17c6b9b10c5045ddaa12ea2b61b46ec1
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