Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1073/pnas.1620290114
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- Co-Autor*innen der Med Uni Graz
- Golob-Schwarzl Nicole
- Haybäck Johannes
- Schweiger Caroline
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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 (using NLM MeSH Indexing)
- Adenomatous Polyposis Coli Protein - genetics
- Adenomatous Polyposis Coli Protein - metabolism
- Adult -
- Aged -
- Animals -
- Carcinogenesis - genetics
- Carcinogenesis - metabolism
- Cell Line, Tumor -
- Colorectal Neoplasms - genetics
- Colorectal Neoplasms - metabolism
- Colorectal Neoplasms - pathology
- Cytokine Receptor gp130 - genetics
- Cytokine Receptor gp130 - metabolism
- Female -
- HCT116 Cells -
- HEK293 Cells -
- HT29 Cells -
- Humans -
- Male -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Mice, Transgenic -
- Middle Aged -
- Mutation -
- Nuclear Proteins - metabolism
- Transcription Factors - metabolism
- beta Catenin - genetics
- beta Catenin - metabolism
- Find related publications in this database (Keywords)
- colorectal cancer
- adenomatous polyposis coli
- IL-6ST/gp130
- YAP
- STAT3