Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer

Authors

Yumeng Wang, University of Texas MD Anderson Cancer Center
Xiaoyan Xu, University of Texas MD Anderson Cancer Center
Dejan Maglic, Children's Hospital Boston
Michael T. Dill, Children's Hospital Boston
Kamalika Mojumdar, University of Texas MD Anderson Cancer Center
Patrick Kwok Shing Ng, University of Texas MD Anderson Cancer Center
Kang Jin Jeong, University of Texas MD Anderson Cancer Center
Yiu Huen Tsang, Baylor College of Medicine
Daniela Moreno, Baylor College of Medicine
Venkata Hemanjani Bhavana, Baylor College of Medicine
Xinxin Peng, University of Texas MD Anderson Cancer Center
Zhongqi Ge, University of Texas MD Anderson Cancer Center
Hu Chen, University of Texas MD Anderson Cancer Center
Jun Li, University of Texas MD Anderson Cancer Center
Zhongyuan Chen, University of Texas MD Anderson Cancer Center
Huiwen Zhang, University of Texas Health Science Center at Houston
Leng Han, University of Texas Health Science Center at Houston
Di Du, University of Texas MD Anderson Cancer Center
Chad J. Creighton, Baylor College of Medicine
Gordon B. Mills, University of Texas MD Anderson Cancer Center
Samantha J. Caesar-Johnson
John A. Demchok
Ina Felau
Melpomeni Kasapi
Martin L. Ferguson
Carolyn M. Hutter
Heidi J. Sofia
Roy Tarnuzzer
Zhining Wang
Liming Yang
Jean C. Zenklusen
Jiashan (Julia) Zhang
Sudha Chudamani

Document Type

Journal Article

Publication Date

10-30-2018

Journal

Cell Reports

Volume

25

Issue

5

DOI

10.1016/j.celrep.2018.10.001

Keywords

driver mutation; miRNA regulation; pan-cancer analysis; pathway activity; prognostic power; TAZ; TCGA; tumor subtype; YAP

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.

APA Citation

Wang, Y., Xu, X., Maglic, D., Dill, M., Mojumdar, K., Ng, P., Jeong, K., Tsang, Y., Moreno, D., Bhavana, V., Peng, X., Ge, Z., Chen, H., Li, J., Chen, Z., Zhang, H., Han, L., Du, D., Creighton, C., Mills, G., Caesar-Johnson, S., Demchok, J., Felau, I., Kasapi, M., Ferguson, M., Hutter, C., Sofia, H., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J., Zhang, J., & Chudamani, S. (2018). Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer. Cell Reports, 25 (5). http://dx.doi.org/10.1016/j.celrep.2018.10.001