title: YAP promotes ovarian cancer cell tumorigenesis and is indicative of a poor prognosis for ovarian cancer patients.
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.
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Neurology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chang
authors.affiliation: Department of Pathology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Yixiong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.affiliation: The Affiliated Guangren Hospital, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, China.
authors.forename: Heng-Yu
authors.initials: HY
authors.lastname: Fan
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002945:Cisplatin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D011379:Prognosis; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D017239:Paclitaxel; D002945:Cisplatin