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PMID: 24622501 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

YAP promotes ovarian cancer cell tumorigenesis and is indicative of a poor prognosis for ovarian cancer patients.

PloS one ·Vol. 9 ·No. 3 ·2014-00-00 ·页码 e91770

Xia Y, Chang T, Wang Y, Liu Y, Li W, Li M, Fan HY

Abstract

YAP is a key component of the Hippo signaling pathway and plays a critical role in the development and progression of multiple cancer types, including ovarian cancer. However, the effects of YAP on ovarian cancer development in vivo and its downstream effectors remain uncertain. In this study we found that strong YAP expression was associated with poor ovarian cancer patient survival. Specifically, we showed for the first time that high YAP expression levels were positively correlated with TEAD4 gene expression, and their co-expression was a prognostic marker for poor ovarian cancer survival. Hyperactivation of YAP by mutating its five inhibitory phosphorylation sites (YAP-5SA) increased ovarian cancer cell proliferation, resistance to chemotherapeutic drugs, cell migration, and anchorage-independent growth. In contrast, expression of a dominant negative YAP mutant reversed these phenotypes in ovarian cancer cells both in vitro and in vivo. Our results suggested that YAP caused these effects by promoting an epithelial-to-mesenchymal transition. Thus, YAP promotes ovarian cancer cell growth and tumorigenesis both in vitro and in vivo. Further, high YAP and TEAD4 expression is a prognostic marker for ovarian cancer progression and a potential target for ovarian cancer treatment.

MeSH 主题词
Active Transport, Cell Nucleus/drug effects Adaptor Proteins, Signal Transducing/metabolism Animals Apoptosis/drug effects Carcinogenesis/drug effects Cell Line, Tumor Cell Movement/drug effects Cell Nucleus/drug effects,metabolism Cell Proliferation/drug effects Cell Transformation, Neoplastic Cisplatin/pharmacology DNA-Binding Proteins/metabolism Drug Resistance, Neoplasm Female Gene Expression Regulation, Neoplastic/drug effects Humans Mice Muscle Proteins/metabolism Ovarian Neoplasms/diagnosis,metabolism,pathology Paclitaxel/pharmacology Phosphoproteins/metabolism Prognosis TEA Domain Transcription Factors Transcription Factors/metabolism YAP-Signaling Proteins
化学物质
Adaptor Proteins, Signal Transducing DNA-Binding Proteins Muscle Proteins Phosphoproteins TEA Domain Transcription Factors TEAD4 protein, human Transcription Factors YAP-Signaling Proteins YAP1 protein, human Paclitaxel Cisplatin
作者与单位
共 7 位作者,点击展开单位 / ORCID
Xia Yan
Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, China.
Chang Ting
Department of Neurology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
Wang Yingmei
Department of Pathology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
Liu Yixiong
Department of Pathology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
Li Wenhui
Department of Obstetrics and Gynecology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
Li Ming
The Affiliated Guangren Hospital, Xi'an Jiaotong University, Xi'an, China.
Fan Heng-Yu
Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, China.
Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
Published
2014-00-00
电子出版
2014-00-12
页码
e91770
Language
English
Country/Region
United States
NLM ID
101285081
勘误 / 撤稿关联
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