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Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer
Authors
Venkata Hemanjani Bhavana
Samantha J. Caesar-Johnson
+31 more
Hu Chen
Zhongyuan Chen
Sudha Chudamani
Chad J. Creighton
John A. Demchok
Michael T. Dill
Di Du
Ina Felau
Martin L. Ferguson
Zhongqi Ge
Leng Han
Carolyn M. Hutter
Kang Jin Jeong
Melpomeni Kasapi
Jun Li
Dejan Maglic
Gordon B. Mills
Kamalika Mojumdar
Daniela Moreno
Patrick Kwok Shing Ng
Xinxin Peng
Heidi J. Sofia
Roy Tarnuzzer
Yiu Huen Tsang
Yumeng Wang
Zhining Wang
Xiaoyan Xu
Liming Yang
Jean C. Zenklusen
Huiwen Zhang
Jiashan (Julia) Zhang
Publication date
30 October 2018
Publisher
Health Sciences Research Commons
Abstract
© 2018 The Authors 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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George Washington University: Health Sciences Research Commons (HSRC)
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Last time updated on 03/12/2020