title: YAP induces high-grade serous carcinoma in fallopian tube secretory epithelial cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: G
authors.initials: G
authors.lastname: Hua
authors.affiliation: Olson Center for Women's Health, Department of Obstetrics/Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: X
authors.initials: X
authors.lastname: Lv
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: He
authors.affiliation: Olson Center for Women's Health, Department of Obstetrics/Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Remmenga
authors.affiliation: Olson Center for Women's Health, Department of Obstetrics/Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Rodabough
authors.affiliation: Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: J
authors.initials: J
authors.lastname: Dong
authors.affiliation: 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.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Lele
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Urumuqi General Hospital of Lanzhou Military Region, Urumuqi, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Karst
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: R I
authors.initials: RI
authors.lastname: Drapkin
authors.affiliation: Olson Center for Women's Health, Department of Obstetrics/Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.|Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.|Omaha Veterans Affairs Medical Center, Omaha, NE, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Davis
authors.affiliation: Olson Center for Women's Health, Department of Obstetrics/Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.|Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005187:Fallopian Tubes / Q000378:metabolism / Q000473:pathology; D005260:Female; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010671:Phenylurea Compounds / Q000008:administration & dosage; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D011166:Porphyrins / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors; D000077362:Verteporfin; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010671:Phenylurea Compounds; D010750:Phosphoproteins; D011166:Porphyrins; D011743:Pyrimidines; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D000077362:Verteporfin; D005346:Fibroblast Growth Factors; C568950:infigratinib