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Comprehensive molecular characterization of the Hippo signaling pathway in cancer

Title: Comprehensive molecular characterization of the Hippo signaling pathway in cancer
Authors: Wang, Y
Xu, X
Maglic, D
Dill, MT
Mojumdar, K
Ng, PK-S
Jeong, KJ
Tsang, YH
Moreno, D
Bhavana, VH
Peng, X
Ge, Z
Chen, H
Li, J
Chen, Z
Zhang, H
Han, L
Du, D
Creighton, CJ
Mills, GB
Camargo, F
Liang, H
Item Type: Journal Article
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.
Issue Date: 30-Oct-2018
Date of Acceptance: 28-Sep-2018
URI: http://hdl.handle.net/10044/1/71212
DOI: https://doi.org/10.1016/j.celrep.2018.10.001
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 1304
End Page: 1317.e5
Journal / Book Title: Cell Reports
Volume: 25
Issue: 5
Copyright Statement: © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Funder's Grant Number: TCGA Pilot Program
15Y011ST
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
ORGAN SIZE CONTROL
PANCREATIC-CANCER
TUMOR PROGRESSION
BREAST-CANCER
YAP
PROMOTES
TAZ
GENE
GROWTH
CELLS
TAZ
TCGA
YAP
driver mutation
miRNA regulation
pan-cancer analysis
pathway activity
prognostic power
tumor subtype
Cancer Genome Atlas Research Network
Science & Technology
Life Sciences & Biomedicine
Cell Biology
ORGAN SIZE CONTROL
PANCREATIC-CANCER
TUMOR PROGRESSION
BREAST-CANCER
YAP
PROMOTES
TAZ
GENE
GROWTH
CELLS
Publication Status: Published
Online Publication Date: 2018-10-30
Appears in Collections:Department of Surgery and Cancer