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Type of publication: Journal Article
Type of document: Full Paper

Year: 2017

Authors: Taniguchi, K; Moroishi, T; de Jong, PR; Krawczyk, M; Grebbin, BM; Luo, H; Xu, RH; Golob-Schwarzl, N; Schweiger, C; Wang, K; Di Caro, G; Feng, Y; Fearon, ER; Raz, E; Kenner, L; Farin, HF; Guan, KL; Haybaeck, J; Datz, C; Zhang, K; Karin, M

Title: YAP-IL-6ST autoregulatory loop activated on APC loss controls colonic tumorigenesis.

Source: Proc Natl Acad Sci U S A. 2017; 114(7):1643-1648

Authors Vetmeduni Vienna:

Kenner Lukas

Vetmed Research Units
Institute of Pathology, Pathology of Laboratory Animals

Loss of tumor suppressor adenomatous polyposis coli (APC) activates β-catenin to initiate colorectal tumorigenesis. However, β-catenin (CTNNB1) activating mutations rarely occur in human colorectal cancer (CRC). We found that APC loss also results in up-regulation of IL-6 signal transducer (IL-6ST/gp130), thereby activating Src family kinases (SFKs), YAP, and STAT3, which are simultaneously up-regulated in the majority of human CRC. Although, initial YAP activation, which stimulates IL6ST gene transcription, may be caused by reduced serine phosphorylation, sustained YAP activation depends on tyrosine phosphorylation by SFKs, whose inhibition, along with STAT3-activating JAK kinases, causes regression of established colorectal tumors. These results explain why APC loss is a more potent initiating event than the mere activation of CTNNB1.

Keywords Pubmed: Adenomatous Polyposis Coli Proteingeneticsmetabolism
Cell Cycle Proteins
Cell Line, Tumor
Colorectal Neoplasmsgeneticsmetabolismpathology
Cytokine Receptor gp130geneticsmetabolism
HCT116 Cells
HEK293 Cells
HT29 Cells
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Middle Aged
Nuclear Proteinsmetabolism
Transcription Factorsmetabolism
beta Cateningeneticsmetabolism

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