TY - JOUR
T1 - Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer
AU - The Cancer Genome Atlas Research Network
AU - Wang, Yumeng
AU - Mojumdar, Kamalika
AU - Peng, Xinxin
AU - Ge, Zhongqi
AU - Li, Jun
AU - Han, Leng
AU - Mills, Gordon B
AU - Liu, Yuexin
AU - Zhang, Wei
AU - Akbani, Rehan
AU - Broom, Bradley M.
AU - Ju, Zhenlin
AU - Kanchi, Rupa Sridevi
AU - Korkut, Anil
AU - Liang, Han
AU - Ling, Shiyun
AU - Liu, Wenbin
AU - Lu, Yiling
AU - Uppore Kukkillaya, Arvind Rao
AU - Wang, Jing
AU - Weinstein, John N.
AU - Zhang, Jiexin
AU - Liu, Xiuping
AU - Wang, Linghua
AU - Carvalho, André L.
AU - Fregnani, José Humberto T. G.
AU - Reis, Rui M. V.
AU - Scapulatempo, Cristovam Neto
AU - Ajani, Jaffer A.
AU - Behrens, Carmen
AU - Bondaruk, Jolanta
AU - Broaddus, Russell
AU - Czerniak, Bogdan
AU - Esmaeli, Bita
AU - Fujimoto, Junya
AU - Gershenwald, Jeffrey
AU - Guo, Charles
AU - Lazar, Alexander J.
AU - Logothetis, Christopher
AU - Meric-Bernstam, Funda
AU - Moran, Cesar
AU - Ramondetta, Lois
AU - Rice, David
AU - Sood, Anil
AU - Tamboli, Pheroze
AU - Thompson, Timothy
AU - Troncoso, Patricia
AU - Tsao, Anne
AU - Wistuba, Ignacio
AU - von Deimling, Andreas
N1 - Publisher Copyright:
© 2018 The Authors
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. 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.
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. 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.
KW - TAZ
KW - TCGA
KW - YAP
KW - driver mutation
KW - miRNA regulation
KW - pan-cancer analysis
KW - pathway activity
KW - prognostic power
KW - tumor subtype
UR - http://www.scopus.com/inward/record.url?scp=85055628471&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055628471&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.10.001
DO - 10.1016/j.celrep.2018.10.001
M3 - Article
C2 - 30380420
AN - SCOPUS:85055628471
SN - 2211-1247
VL - 25
SP - 1304-1317.e5
JO - Cell Reports
JF - Cell Reports
IS - 5
ER -