Kang W, Cheng AS, Yu J, To KF. Emerging role of Hippo pathway in gastric and other gastrointestinal cancers. World J Gastroenterol 2016; 22(3): 1279-1288 [PMID: 26811664 DOI: 10.3748/wjg.v22.i3.1279]
Corresponding Author of This Article
Ka Fai To, Professor, Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Center, Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. kfto@cuhk.edu.hk
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jan 21, 2016; 22(3): 1279-1288 Published online Jan 21, 2016. doi: 10.3748/wjg.v22.i3.1279
Emerging role of Hippo pathway in gastric and other gastrointestinal cancers
Wei Kang, Alfred SL Cheng, Jun Yu, Ka Fai To
Wei Kang, Ka Fai To, Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Center, Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
Alfred SL Cheng, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
Jun Yu, Department of Medicine and Therapeutics, Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
Author contributions: To KF provided direction and guidance throughout the preparation of this manuscript; Kang W conducted the literature review and drafted the manuscript; Cheng ASL and Yu J reviewed the manuscript and made significant revisions on the drafts.
Supported by General Research Fund (No. 2140855, RGC Reference No. CUHK14114414) from The Research Grants Council of Hong Kong, National Natural Science Grant No. 81201591 from China, and Direct Grant for Research No. 2014.2.002 from The Chinese University of Hong Kong.
Conflict-of-interest statement: The authors report no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ka Fai To, Professor, Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Center, Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. kfto@cuhk.edu.hk
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Received: April 28, 2015 Peer-review started: May 5, 2015 First decision: June 23, 2015 Revised: July 15, 2015 Accepted: November 13, 2015 Article in press: November 13, 2015 Published online: January 21, 2016 Processing time: 261 Days and 22.6 Hours
Abstract
More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1 (YAP1) and its close paralog TAZ, transcriptional co-activator with a PDZ-binding motif, function as key effectors negatively controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In various cancers, Hippo pathway cross-talks with pro- or anti-tumorigenic pathways such as GPCR, Wnt/β-catenin, Notch and TGF-β signaling and is deregulated by multiple factors including cell density/junction and microRNAs. As YAP1 expression is significantly associated with poor prognosis of gastric and other gastrointestinal cancers, detailed delineation of Hippo regulation in tumorigenesis provides novel insight for therapeutic intervention. In current review, we summarized the recent research progresses on the deregulation of Hippo pathway in the gastrointestinal tract including stomach and discuss the molecular consequences leading to tumorigenesis.
Core tip: Hippo signaling pathway is a gradually emerging pathway that plays a necessary role in homeostasis of gastrointestinal tissues, whereas its deregulation frequently induces the occurrence of cancers. In gastric and other gastrointestinal cancers, the upstream components of Hippo pathway often show decreased expression and their downregulation loses the inhibitory effect on yes-associated protein 1 (YAP1)/TAZ. Thus YAP1/TAZ is translocated into the nucleus and exerts oncogenic function by direct binding with TEAD transcription factors to activate the downstream targets transcriptionally. In this brief review, we summarize the deregulation of Hippo pathway in gastric and other gastrointestinal cancers.
