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

G. Hua, X. Lv, C. He, Steven W Remmenga, K. J. Rodabough, Jixin Dong, L. Yang, Subodh M Lele, P. Yang, J. Zhou, A. Karst, R. I. Drapkin, John S Davis, C. Wang

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28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2247-2265
Number of pages19
JournalOncogene
Volume35
Issue number17
DOIs
StatePublished - Apr 28 2016

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Hua, G., Lv, X., He, C., Remmenga, S. W., Rodabough, K. J., Dong, J., Yang, L., Lele, S. M., Yang, P., Zhou, J., Karst, A., Drapkin, R. I., Davis, J. S., & Wang, C. (2016). YAP induces high-grade serous carcinoma in fallopian tube secretory epithelial cells. Oncogene, 35(17), 2247-2265. https://doi.org/10.1038/onc.2015.288