Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer
Standard
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; Cancer Genome Atlas Research Network.
in: CELL REP, Jahrgang 25, Nr. 5, 30.10.2018, S. 1304-1317.e5.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer
AU - Wang, Yumeng
AU - Xu, Xiaoyan
AU - Maglic, Dejan
AU - Dill, Michael T
AU - Mojumdar, Kamalika
AU - Ng, Patrick Kwok-Shing
AU - Jeong, Kang Jin
AU - Tsang, Yiu Huen
AU - Moreno, Daniela
AU - Bhavana, Venkata Hemanjani
AU - Peng, Xinxin
AU - Ge, Zhongqi
AU - Chen, Hu
AU - Li, Jun
AU - Chen, Zhongyuan
AU - Zhang, Huiwen
AU - Han, Leng
AU - Du, Di
AU - Creighton, Chad J
AU - Mills, Gordon B
AU - Camargo, Fernando
AU - Liang, Han
AU - Cancer Genome Atlas Research Network
AU - Sauter, Guido
N1 - Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2018/10/30
Y1 - 2018/10/30
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.celrep.2018.10.001
DO - 10.1016/j.celrep.2018.10.001
M3 - SCORING: Journal article
C2 - 30380420
VL - 25
SP - 1304-1317.e5
JO - CELL REP
JF - CELL REP
SN - 2211-1247
IS - 5
ER -