19840 Onkologi 3_17 - Onkologi i Sverige

Hoxgeners roll i stamcellsdifferentiering och cancer

Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. The Wnt target gene Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) marks actively dividing stem cells in Wnt-driven, self-renewing tissues such as small intestine and colon, stomach and hair follicles. A three-dimensional culture system allows long-term clonal expansion of single … Lgr5 is a receptor for R-spondins (de Lau et al., 2011) that activate the frizzled-Lrp5/6 complex in conjunction with Wnt and is a marker for adult stem cells in the colon and small intestine (Barker et al., 2007). LGR5 is a member of the Wnt signaling pathway.

Results. LGR5 + cells possessed stronger stemness properties compared to LGR5 − cells. TGFβ1 additive activates LGR5, CEACAM6 and Wnt signaling after CD151 silencing. A and B. Western blot and qRT-PCR showed TGFβ1, LGR5, CEACAM6, Wnt3a and Wnt5a were remarkably upregulated at both protein and mRNA levels after treatment with TGFβ1 at 0.05, 0.10 and 0.50 ng/ml, respectively, on sh-CD151 transfected HT29 cells (sh-CD151+TGFβ1 group versus sh-CD151 group).

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TGFβ1 additive activates LGR5, CEACAM6 and Wnt signaling after CD151 silencing. A and B. Western blot and qRT-PCR showed TGFβ1, LGR5, CEACAM6, Wnt3a and Wnt5a were remarkably upregulated at both protein and mRNA levels after treatment with TGFβ1 at 0.05, 0.10 and 0.50 ng/ml, respectively, on sh-CD151 transfected HT29 cells (sh-CD151+TGFβ1 group versus sh-CD151 group). The treatment experiment was performed in an intracranial orthotopic xenograft model by knockdown of LGR5 or by using the Wnt/β-catenin pathway inhibitor Wnt-C59.

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However, whether LGR5 and LGR4 are coupled to other intracellular signaling pathways to regulate stem cell function remains unknown. The Wnt/β-catenin signaling system plays essential roles in embryonic development and in the self-renewal and maintenance of adult stem cells. R-spondins (RSPOs) are a group of secreted proteins that enhance Wnt/β-catenin signaling and have pleiotropic functions in development and stem cell growth. LGR5, an orphan receptor of the G protein-coupled receptor (GPCR) superfamily, is specifically 2018-01-09 · Background The WNT pathway regulates intestinal stem cells and is frequently disrupted in intestinal adenomas. The pathway contains several potential biotargets for interference, including the poly-ADP ribosyltransferase enzymes tankyrase1 and 2. LGR5 is a known WNT pathway target gene and marker of intestinal stem cells.

2019-07-29 Abstract. Lgr5 was originally discovered as a common Wnt target gene in adult intestinal crypts and colon cancer. It was subsequently identified as an exquisite marker of multiple Wnt-driven adult stem cell types. Lgr5 and its homologs, Lgr4 and Lgr6, constitute the receptors for R-spondins, potent Wnt signal enhancers and stem cell growth factors.
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R‐spondin – inducible CreERT2 fusion protein into the Lgr5 locus, a Wnt target gene exquisitely expressed in crypt base columnar cells.16 These cells divide every 24 hours, 20.

Wnt-signalering är en nödvändig drivkraft för den totala Clevers H (2015): Wnt signaling, Lgr5 stem cells, organoids and cancer. 6h 43. 2K.
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Hoxgeners roll i stamcellsdifferentiering och cancer

2009). To determine whether Lgr5 expression is also modulated by Wnt signaling in the inner ear, we tested the effects of Wnt agonist and antagonist on cochlear explants. 2010-01-08 · The Wnt target gene Lgr5 marks stem cells in the small intestine, colon, and hair follicle. Here, we investigated Lgr5 expression in the stomach and assessed the stem cell potential of the Lgr5 +ve cells by using in vivo lineage tracing. Also, in contrast to flow-sorted Lgr5 high and low cells from AOM/DSS-induced tumors, the Wnt signaling pathway was not significantly altered in our loss-of-function experiments in cell lines, though tending to be higher in LGR5 high spheres compared with LGR5 low adherent cells (P = 0.16). Lgr5 homologues are facultative Wnt receptor components that mediate Wnt signal enhancement by soluble R-spondin proteins.