| Literature DB >> 28130546 |
Koji Taniguchi1,2,3,4,5, Toshiro Moroishi6, Petrus R de Jong7,8, Michal Krawczyk9, Britta Moyo Grebbin10,11,12, Huiyan Luo9,13, Rui-Hua Xu13, Nicole Golob-Schwarzl14, Caroline Schweiger14, Kepeng Wang1,2,3,15, Giuseppe Di Caro1,2,3, Ying Feng16, Eric R Fearon16,17,18, Eyal Raz7, Lukas Kenner19,20,21, Henner F Farin10,11,12, Kun-Liang Guan6, Johannes Haybaeck14,22, Christian Datz23, Kang Zhang9, Michael Karin24,2,3,25.
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.Entities:
Keywords: IL-6ST/gp130; STAT3; YAP; adenomatous polyposis coli; colorectal cancer
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Year: 2017 PMID： 28130546 PMCID： PMC5320959 DOI： 10.1073/pnas.1620290114
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205