YAP Induces High-Grade Serous Carcinoma in Fallopian Tube Secretory Epithelial Cells

Autor: Guohua Hua, Jin Zhou, Chunbo He, Jixin Dong, Cheng Wang, John S. Davis, Peixin Yang, Liguo Yang, Ronny Drapkin, Alison M. Karst, Subodh M. Lele, Kerry J. Rodabough, Steven W. Remmenga, Xiangmin Lv
Jazyk: angličtina
Rok vydání: 2015
Předmět:
0301 basic medicine
Cancer Research
endocrine system
animal structures
Porphyrins
Serous carcinoma
Carcinogenesis
Biology
Bioinformatics
medicine.disease_cause
Fibroblast growth factor
Article
03 medical and health sciences
Cell Movement
Genetics
medicine
Fallopian Tube Neoplasms
Humans
Receptor
Autocrine signalling
Molecular Biology
Fallopian Tubes
Adaptor Proteins
Signal Transducing
Cell Proliferation
Ovarian Neoplasms
Cell growth
Phenylurea Compounds
Verteporfin
Epithelial Cells
YAP-Signaling Proteins
medicine.disease
Phosphoproteins
female genital diseases and pregnancy complications
3. Good health
Cystadenocarcinoma
Serous
Fibroblast Growth Factors
Gene Expression Regulation
Neoplastic
030104 developmental biology
medicine.anatomical_structure
Pyrimidines
Cancer research
Female
Signal transduction
Neoplasm Grading
Fallopian tube
Signal Transduction
Transcription Factors
Zdroj: Oncogene
ISSN: 1476-5594
0950-9232
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: