YAP induces high-grade serous carcinoma in fallopian tube secretory epithelial cells.
Oncogene
; 35(17): 2247-65, 2016 04 28.
Article
em En
| MEDLINE
| ID: mdl-26364602
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Fosfoproteínas
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Cistadenocarcinoma Seroso
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Proteínas Adaptadoras de Transdução de Sinal
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Neoplasias das Tubas Uterinas
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Carcinogênese
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article