Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer
01 Pubblicazione su rivista
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., Caesar-Johnson Samantha J., Demchok John A., Felau Ina, Kasapi Melpomeni, Ferguson Martin L., Hutter Carolyn M., Sofia Heidi J., Tarnuzzer Roy, Wang Zhining, Yang Liming, Zenklusen Jean C., Zhang Jiashan (Julia), Chudamani Sudha, Liu Jia, Lolla Laxmi, Naresh Rashi, Pihl Todd, Sun Qiang, Wan Yunhu, Wu Ye, Cho Juok, Defreitas Timothy, Frazer Scott, Gehlenborg Nils, Getz Gad, Heiman David I., Kim Jaegil, Lawrence Michael S., Lin Pei, Meier Sam, Noble Michael S., Saksena Gordon, Voet Doug, Zhang Hailei, Bernard Brady, Chambwe Nyasha, Dhankani Varsha, Knijnenburg Theo, Kramer Roger, Leinonen Kalle, Liu Yuexin, Miller Michael, Reynolds Sheila, Shmulevich Ilya, Thorsson Vesteinn, Zhang Wei, Akbani Rehan, Broom Bradley M., Hegde Apurva M., Ju Zhenlin, Kanchi Rupa S., Korkut Anil, Li Jun, Liang Han, Ling Shiyun, Liu Wenbin, Lu Yiling, Mills Gordon B., Ng Kwok-Shing, Rao Arvind, Ryan Michael, Wang Jing, Weinstein John N., Zhang Jiexin, Abeshouse Adam, Armenia Joshua, Chakravarty Debyani, Chatila Walid K., de Bruijn Ino, Gao Jianjiong, Gross Benjamin E., Heins Zachary J., Kundra Ritika, La Konnor, Ladanyi Marc, Luna Augustin, Nissan Moriah G., Ochoa Angelica, Phillips Sarah M., Reznik Ed, Sanchez-Vega Francisco, Sander Chris, Schultz Nikolaus, Sheridan Robert, Sumer S. Onur, Sun Yichao, Taylor Barry S., Wang Jioajiao, Zhang Hongxin, Anur Pavana, Peto Myron, Spellman Paul, Benz Christopher, Stuart Joshua M., Wong Christopher K., Yau Christina, Hayes D. Neil, Parker Joel S., Wilkerson Matthew D., Ally Adrian, Balasundaram Miruna, Bowlby Reanne, Brooks Denise, Carlsen Rebecca, Chuah Eric, Dhalla Noreen, Holt Robert, Jones Steven J. M., Kasaian Katayoon, Lee Darlene, Ma Yussanne, Marra Marco A., Mayo Michael, Moore Richard A., Mungall Andrew J., Mungall Karen, Robertson A. Gordon, Sadeghi Sara, Schein Jacqueline E., Sipahimalani Payal, Tam Angela, Thiessen Nina, Tse Kane, Wong Tina, Berger Ashton C., Beroukhim Rameen, Cherniack Andrew D., Cibulskis Carrie, Gabriel Stacey B., Gao Galen F., Ha Gavin, Meyerson Matthew, Schumacher Steven E., Shih Juliann, Kucherlapati Melanie H., Kucherlapati Raju S., Baylin Stephen, Cope Leslie, Danilova Ludmila, Bootwalla Moiz S., Lai Phillip H., Maglinte Dennis T., Van Den Berg David J., Weisenberger Daniel J., Auman J. Todd, Balu Saianand, Bodenheimer Tom, Fan Cheng, Hoadley Katherine A., Hoyle Alan P., Jefferys Stuart R., Jones Corbin D., Meng Shaowu, Mieczkowski Piotr A., Mose Lisle E., Perou Amy H., Perou Charles M., Roach Jeffrey, Shi Yan, Simons Janae V., Skelly Tara, Soloway Matthew G., Tan Donghui, Veluvolu Umadevi, Fan Huihui, Hinoue Toshinori, Laird Peter W., Shen Hui, Zhou Wanding, Bellair Michelle, Chang Kyle, Covington Kyle, Creighton Chad J., Dinh Huyen, Doddapaneni Harshavardhan, Donehower Lawrence A., Drummond Jennifer, Gibbs Richard A., Glenn Robert, Hale Walker, Han Yi, Hu Jianhong, Korchina Viktoriya, Lee Sandra, Lewis Lora, Li Wei, Liu Xiuping, Morgan Margaret, Morton Donna, Muzny Donna, Santibanez Jireh, Sheth Margi, Shinbrot Eve, Wang Linghua, Wang Min, Wheeler David A., Xi Liu, Zhao Fengmei, Hess Julian, Appelbaum Elizabeth L., Bailey Matthew, Cordes Matthew G., Ding Li, Fronick Catrina C., Fulton Lucinda A., Fulton Robert S., Kandoth Cyriac, Mardis Elaine R., Mclellan Michael D., Miller Christopher A., Schmidt Heather K., Wilson Richard K., Crain Daniel, Curley Erin, Gardner Johanna, Lau Kevin, Mallery David, Morris Scott, Paulauskis Joseph, Penny Robert, Sh
ISSN: 2211-1247
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.