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Oncogene. 2016 Apr 28;35(17):2247-65. doi: 10.1038/onc.2015.288. Epub 2015 Sep 14.

YAP induces high-grade serous carcinoma in fallopian tube secretory epithelial cells.

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Olson Center for Women's Health, Department of Obstetrics/Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.
The Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.
Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Obstetrics and Gynecology, Urumuqi General Hospital of Lanzhou Military Region, Urumuqi, China.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Omaha Veterans Affairs Medical Center, Omaha, NE, USA.


Accumulating evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from fallopian tube secretory epithelial cells (FTSECs). However, the molecular mechanisms underlying the initiation and progression of HGSC derived from FTSECs remains unclear. In this study, we found that the Hippo/Yes-associated protein (YAP) signaling pathway has a critical role in the initiation and progression of fallopian tube and ovarian HGSC. Importantly, YAP was overexpressed in inflammatory and cancerous fallopian tube tissues. Further, overexpression of wild-type YAP, or constitutively active YAP in immortalized FTSECs, induced cell proliferation, migration, colony formation and tumorigenesis. Moreover, the Hippo/YAP and the fibroblast growth factor (FGF) signaling pathways formed an autocrine/paracrine-positive feedback loop to drive the progression of the FTSEC-derived HGSC. Evidence in this study strongly suggests that combined therapy with inhibitors of YAP (such as verteporfin) and FGF receptors (such as BGJ398) can provide a novel therapeutic strategy to treat fallopian tube and ovarian HGSC.

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