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YAP-IL-6ST autoregulatory loop activated on APC loss controls colonic tumorigenesis.
Taniguchi, Koji; Moroishi, Toshiro; de Jong, Petrus R; Krawczyk, Michal; Grebbin, Britta Moyo; Luo, Huiyan; Xu, Rui-Hua; Golob-Schwarzl, Nicole; Schweiger, Caroline; Wang, Kepeng; Di Caro, Giuseppe; Feng, Ying; Fearon, Eric R; Raz, Eyal; Kenner, Lukas; Farin, Henner F; Guan, Kun-Liang; Haybaeck, Johannes; Datz, Christian; Zhang, Kang; Karin, Michael.
Afiliación
  • Taniguchi K; Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, CA 92093.
  • Moroishi T; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093.
  • de Jong PR; Department of Pathology, University of California, San Diego, La Jolla, CA 92093.
  • Krawczyk M; Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
  • Grebbin BM; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
  • Luo H; Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093.
  • Xu RH; Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093.
  • Golob-Schwarzl N; Sanford Burnham Prebys Medical Discovery Institute, National Cancer Institute-Designated Cancer Center, La Jolla, CA 92037.
  • Schweiger C; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093.
  • Wang K; German Cancer Consortium, 69120 Heidelberg, Germany.
  • Di Caro G; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt on Main, Germany.
  • Feng Y; German Cancer Research Center, 69120 Heidelberg, Germany.
  • Fearon ER; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093.
  • Raz E; State Key Laboratory of Oncology, Sun Yat-sen University Cancer Center, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
  • Kenner L; State Key Laboratory of Oncology, Sun Yat-sen University Cancer Center, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
  • Farin HF; Institute of Pathology, Medical University of Graz, Graz A-8036, Austria.
  • Guan KL; Institute of Pathology, Medical University of Graz, Graz A-8036, Austria.
  • Haybaeck J; Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, CA 92093.
  • Datz C; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093.
  • Zhang K; Department of Pathology, University of California, San Diego, La Jolla, CA 92093.
  • Karin M; Department of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT, 06030.
Proc Natl Acad Sci U S A ; 114(7): 1643-1648, 2017 02 14.
Article en En | MEDLINE | ID: mdl-28130546
Loss of tumor suppressor adenomatous polyposis coli (APC) activates ß-catenin to initiate colorectal tumorigenesis. However, ß-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas Nucleares / Neoplasias Colorrectales / Proteína de la Poliposis Adenomatosa del Colon / Receptor gp130 de Citocinas Límite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas Nucleares / Neoplasias Colorrectales / Proteína de la Poliposis Adenomatosa del Colon / Receptor gp130 de Citocinas Límite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos