Zeitschriftenaufsatz
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2017
YAP-IL-6ST autoregulatory loop activated on APC loss controls colonic tumorigenesis
Autor:in
Taniguchi, Koji; Moroishi, Toshiro; DeJong, Petrus; Krawczyk, Michał; Grebbin, Britta M.; 骆, 卉妍; Xu, Rui-Hua; Golob-Schwarzl, Nicole; Schweiger, Caroline M.; Wang, Kepeng; Di Caroa, Giuseppe; Feng, Ying; Fearon, Eric R.; Raz, Eyal; Kenner, Lukas; Farin, Henner; Guan, Kun-Liang; Haybaeck, Johannes; Datz, Christian; Zhang, Kang; Karin, Michael
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Abstrakt
Loss of tumor suppressor adenomatous polyposis coli (APC) activates beta-catenin to initiate colorectal tumorigenesis. However, beta-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.
Schlagwörter
colorectal cancer; adenomatous polyposis coli; IL-6ST/gp130; YAP; STAT3
Dokumententyp
Originalarbeit
Open Access Type
Green
ISSN/eISSN
0027-8424 - 1091-6490
10.1073/pnas.1620290114
WoS ID
PubMed ID