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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

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.
YAP-IL-6ST autoregulatory loop activated on APC loss controls colonic tumorigenesis.
Proc Natl Acad Sci U S A. 2017; 114(7):1643-1648 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Golob-Schwarzl Nicole
Haybäck Johannes
Schweiger Caroline Margarete
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Abstract:
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.

Find related publications in this database (Keywords)
colorectal cancer
adenomatous polyposis coli
IL-6ST/gp130
YAP
STAT3
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