Journal article
Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer
Cell reports (Cambridge), Vol.25(5), pp.1304-1317.e5
10/30/2018
DOI: 10.1016/j.celrep.2018.10.001
PMCID: PMC6326181
PMID: 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.
Details
- Title: Subtitle
- Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer
- Creators
- Yumeng Wang - The University of Texas MD Anderson Cancer CenterXiaoyan Xu - The University of Texas MD Anderson Cancer CenterDejan MaglicMichael T DillKamalika Mojumdar - The University of Texas MD Anderson Cancer CenterPatrick Kwok-Shing Ng - The University of Texas MD Anderson Cancer CenterKang Jin Jeong - The University of Texas MD Anderson Cancer CenterYiu Huen Tsang - Baylor College of MedicineDaniela Moreno - Baylor College of MedicineVenkata Hemanjani Bhavana - Baylor College of MedicineXinxin Peng - The University of Texas MD Anderson Cancer CenterZhongqi Ge - The University of Texas MD Anderson Cancer CenterHu Chen - The University of Texas MD Anderson Cancer CenterJun Li - The University of Texas MD Anderson Cancer CenterZhongyuan Chen - The University of Texas MD Anderson Cancer CenterHuiwen Zhang - The University of Texas Health Science Center at HoustonLeng Han - The University of Texas Health Science Center at HoustonDi Du - The University of Texas MD Anderson Cancer CenterChad J Creighton - Baylor College of MedicineGordon B Mills - The University of Texas MD Anderson Cancer CenterFernando CamargoHan Liang - The University of Texas MD Anderson Cancer Center
- Contributors
- Cancer Genome Atlas Research NetworkDeqin Ma - University of Iowa, PathologyMohammed M Milhem - University of Iowa, Internal MedicineAaron D Bossler - University of Iowa, Pathology
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.25(5), pp.1304-1317.e5
- DOI
- 10.1016/j.celrep.2018.10.001
- PMID
- 30380420
- PMCID
- PMC6326181
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Grant note
- P30 CA016672 / NCI NIH HHS P30 DK034854 / NIDDK NIH HHS R50 CA221675 / NCI NIH HHS U24 CA210950 / NCI NIH HHS U24 CA143883 / NCI NIH HHS U01 CA217842 / NCI NIH HHS U24 CA210949 / NCI NIH HHS R01 CA175486 / NCI NIH HHS U24 CA209851 / NCI NIH HHS
- Language
- English
- Date published
- 10/30/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
- Record Identifier
- 9984185280702771
Metrics
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