标题:CCNG1 (Cyclin G1) regulation by mutant-P53 via induction of Notch3 expression promotes high-grade serous ovarian cancer (HGSOC) tumorigenesis and progression
作者:Xu Y.; Zhang Q.; Miao C.; Dongol S.; Li Y.; Jin C.; Dong R.; Li Y.;等 更多
作者机构:[Xu, Y] Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji'nan, China, Gynecology Oncology Key Laboratory, Qilu Hospital, 更多
通讯作者:Kong, B(kongbeihua@sdu.edu.cn)
通讯作者地址:[Kong, B] Department of Obstetrics and Gynecology, Qilu Hospital, Shandong UniversityChina;
来源:Cancer Medicine
出版年:2018
DOI:10.1002/cam4.1812
关键词:Cyclin G1; high-grade serous ovarian cancer; metastasis; Notch3; P53mt; prognosis
摘要:TP53 mutation is considerably common in advanced high-grade serous ovarian cancer (HGSOC) and significantly associated with a poor prognosis. In this study, we investigated the role of Cyclin G1 (CCNG1), a target gene of wild-type TP53 (P53wt), in HGSOC and the possible regulatory mechanism between TP53 mutant (P53mt) and CCNG1 in the progression of HGSOC. High expression level of CCNG1 was found in 61.3% of HGSOC tissues and only 18.2% in fimbriae of fallopian tubes. Additionally, overexpression of CCNG1 was significantly associated with a shorter overall survival (P < 0.0001) and progression-free survival (P < 0.0004) in HGSOC patients. In vitro, CCNG1 promoted both tumor cell motility by inducing epithelial-mesenchymal transition (EMT) and resistance to cisplatin (CDDP). In vivo, knockdown expression of CCNG1 inhibited cancer metastasis. Furthermore, P53mt increased the expression of CCNG1 by regulating Notch3 expression, and a positive correlation between CCNG1 and Notch3 protein expression was observed by Immunohistochemistry (IHC) (r = 0.39, P: 0.01528). In conclusion, the activation of P53mt-Notch3-CCNG1 pathway was responsible for tumor progression to advanced disease with correlation with worse prognosis in patients with HGSOC. These data suggest a possible molecular mechanism of disease and highlights CCNG1’s potential role as a therapeutic target in HGSOC. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
收录类别:SCOPUS
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85058711387&doi=10.1002%2fcam4.1812&partnerID=40&md5=3c8c76f2c4c382a545cced016cbffa1e
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