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Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer.
Wang, Yumeng; Xu, Xiaoyan; Maglic, Dejan; Dill, Michael T; Mojumdar, Kamalika; Ng, Patrick Kwok-Shing; Jeong, Kang Jin; Tsang, Yiu Huen; Moreno, Daniela; Bhavana, Venkata Hemanjani; Peng, Xinxin; Ge, Zhongqi; Chen, Hu; Li, Jun; Chen, Zhongyuan; Zhang, Huiwen; Han, Leng; Du, Di; Creighton, Chad J; Mills, Gordon B; Camargo, Fernando; Liang, Han.
Afiliación
  • Wang Y; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA.
  • Xu X; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathophysiology, College of Basic Medicine Science, China Medical University, Shenyang, Liaoning Province 110122, China.
  • Maglic D; Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Boston, MA 02115, USA.
  • Dill MT; Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Boston, MA 02115, USA.
  • Mojumdar K; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Ng PK; Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Jeong KJ; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Tsang YH; Department of Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Moreno D; Department of Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Bhavana VH; Department of Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Peng X; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Ge Z; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Chen H; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA.
  • Li J; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Chen Z; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Statistics, Rice University, Houston, TX 77005, USA.
  • Zhang H; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, USA.
  • Han L; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, USA.
  • Du D; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Creighton CJ; Duncan Cancer Center-Biostatistics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Mills GB; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Camargo F; Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Boston, MA 02115, USA. Electronic address: fernando.camargo@childrens.harvard.edu.
  • Liang H; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA; Department of Systems Biology, The University of Texa
Cell Rep ; 25(5): 1304-1317.e5, 2018 10 30.
Article en En | MEDLINE | ID: mdl-30380420
ABSTRACT
Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional "omic" data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas Serina-Treonina Quinasas / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas Serina-Treonina Quinasas / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos