Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer

The Cancer Genome Atlas Research Network

Research output: Contribution to journalArticle

12 Citations (Scopus)

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. Wang et al. perform a comprehensive analysis of 19 Hippo core genes across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. They characterize Hippo pathway activity by a YAP/TAZ transcriptional target signature of 22 genes and highlight the importance of Hippo signaling in squamous cell cancers.

Original languageEnglish (US)
Pages (from-to)1304-1317.e5
JournalCell Reports
Volume25
Issue number5
DOIs
StatePublished - Oct 30 2018

Fingerprint

Genes
Neoplasms
Squamous Cell Neoplasms
Tumors
Atlases
MicroRNAs
Genome
Amplification
Systems Biology
Mutation
Epithelial Cells

Keywords

  • driver mutation
  • miRNA regulation
  • pan-cancer analysis
  • pathway activity
  • prognostic power
  • TAZ
  • TCGA
  • tumor subtype
  • YAP

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer. / The Cancer Genome Atlas Research Network.

In: Cell Reports, Vol. 25, No. 5, 30.10.2018, p. 1304-1317.e5.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Research Network. / Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer. In: Cell Reports. 2018 ; Vol. 25, No. 5. pp. 1304-1317.e5.
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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. Wang et al. perform a comprehensive analysis of 19 Hippo core genes across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. They characterize Hippo pathway activity by a YAP/TAZ transcriptional target signature of 22 genes and highlight the importance of Hippo signaling in squamous cell cancers.",
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KW - driver mutation

KW - miRNA regulation

KW - pan-cancer analysis

KW - pathway activity

KW - prognostic power

KW - TAZ

KW - TCGA

KW - tumor subtype

KW - YAP

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