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The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumourigenesis.

Authors: Tsuji, Shinnosuke  Kawasaki, Yoshihiro  Furukawa, Shiori  Taniue, Kenzui  Hayashi, Tomoatsu  Okuno, Masumi  Hiyoshi, Masaya  Kitayama, Joji  Akiyama, Tetsu 
Citation: Tsuji S, etal., Nat Commun. 2014;5:3150. doi: 10.1038/ncomms4150.
Pubmed: (View Article at PubMed) PMID:24452072
DOI: Full-text: DOI:10.1038/ncomms4150

Aberrant activation of Wnt signalling results in colorectal tumours. Lgr5 is specifically expressed in stem cells of the intestine and has an essential role in maintaining tissue homeostasis. Lgr5-positive stem cells are responsible for the intestinal adenoma initiated by mutations in adenomatous polyposis coli. Furthermore, Lgr5 interacts with R-spondins and thereby activates Wnt signalling. However, the function of Lgr5 in colorectal tumourigenesis is unclear. Here we show that LGR5 is required for the tumourigenicity of colorectal cancer cells. We show that the transcription factor GATA6 directly enhances the expression of LGR5. We further demonstrate that GATA6 is upregulated in colorectal cancer cells due to the downregulation of miR-363, which directly targets GATA6. Moreover, we show that overexpression of miR-363 suppresses the tumourigenicity of colorectal cancer cells. These results suggest that the miR-363-GATA6-LGR5 pathway is critical for colorectal tumourigenesis and would be a promising target for the treatment of colorectal cancer.


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CRRD Object Information
CRRD ID: 13208874
Created: 2017-08-22
Species: All species
Last Modified: 2017-08-22
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.