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

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

doi:10.1038/onc.2015.288

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

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

Research output: Contribution to journal › Article › peer-review

60 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 language	English (US)
Pages (from-to)	2247-2265
Number of pages	19
Journal	Oncogene
Volume	35
Issue number	17
DOIs	https://doi.org/10.1038/onc.2015.288
State	Published - Apr 28 2016

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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10.1038/onc.2015.288

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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.",

author = "G. Hua and X. Lv and C. He and Remmenga, {S. W.} and Rodabough, {K. J.} and J. Dong and L. Yang and Lele, {S. M.} and P. Yang and J. Zhou and A. Karst and Drapkin, {R. I.} and Davis, {J. S.} and C. Wang",

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doi = "10.1038/onc.2015.288",

language = "English (US)",

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AU - Hua, G.

AU - Lv, X.

AU - He, C.

AU - Remmenga, S. W.

AU - Rodabough, K. J.

AU - Dong, J.

AU - Yang, L.

AU - Lele, S. M.

AU - Yang, P.

AU - Zhou, J.

AU - Karst, A.

AU - Drapkin, R. I.

AU - Davis, J. S.

AU - Wang, C.

PY - 2016/4/28

Y1 - 2016/4/28

N2 - 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.

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

Abstract

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