RRC ID 35798
著者 Tsuji S, Kawasaki Y, Furukawa S, Taniue K, Hayashi T, Okuno M, Hiyoshi M, Kitayama J, Akiyama T.
タイトル The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumourigenesis.
ジャーナル Nat Commun
Abstract 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.
巻・号 5
ページ 3150
公開日 2014-1-1
DOI 10.1038/ncomms4150
PII ncomms4150
PMID 24452072
MeSH Carcinogenesis* GATA6 Transcription Factor / metabolism* Humans MicroRNAs / metabolism* Receptors, G-Protein-Coupled / metabolism*
IF 12.121
引用数 54
WOS 分野 CELL BIOLOGY
リソース情報
遺伝子材料 pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393).