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

• Published in: PloS one 2014-03, Vol.9 (3), p.e91770
• Main Authors: Xia, Yan, Chang, Ting, Wang, Yingmei, Liu, Yixiong, Li, Wenhui, Li, Ming, Fan, Heng-Yu
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus - drug effects; Adaptor Proteins, Signal Transducing - metabolism; Animals; Apoptosis; Apoptosis - drug effects; Biology; Cancer; Cancer research; Cancer therapies; Carcinogenesis - drug effects; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cell proliferation; Cell Proliferation - drug effects; Cell Transformation, Neoplastic; Chemotherapy; Cisplatin - pharmacology; DNA-Binding Proteins - metabolism; Drug resistance; Drug Resistance, Neoplasm; Drugs; Female; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Humans; In vivo methods and tests; Kinases; Laboratory animals; Life sciences; Liver cancer; Medical prognosis; Medicine; Mesenchyme; Mice; Muscle Proteins - metabolism; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Paclitaxel - pharmacology; Pathology; Patients; Phosphoproteins - metabolism; Phosphorylation; Prognosis; Proteins; Signal transduction; Signaling; Survival; Transcription factors; Transcription Factors - metabolism; Tumorigenesis; Tumors; Yes-associated protein
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0091770

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.