OCT4 mediates FSH-induced epithelial-mesenchymal transition and invasion through the ERK1/2 signaling pathway in epithelial ovarian cancer.
Our previous study showed that Octamer-binding transcription factor 4 (OCT4) expression was upregulated and significantly associated with histological grade through the analysis of OCT4 expression in 159 ovarian cancer tissue samples, and OCT4 mediated follicle-stimulating hormone (FSH)-induced anti-apoptosis in epithelial ovarian cancer. Nevertheless, whether OCT4 participates in FSH-induced invasion in ovarian cancer is still unknown. Therefore, the present study aimed to define whether FSH-induced ovarian cancer invasion is mediated by OCT4. In present study, we showed that FSH induced not only the epithelial-mesenchymal transition (EMT) and invasive phenotype but also the upregulation of OCT4 expression in a dose- and time-dependent manner in epithelial ovarian cancer cells. In addition, the expression of FSH receptor (FSHR) was upregulated by FSH induction, and knockdown of FSHR inhibited FSH-stimulated OCT4 expression. ERK1/2 signaling pathway participated in the enhanced expression of OCT4 and Snail induced by FSH. We further showed that the activated expression of Snail and N-cadherin, the suppressed expression of E-cadherin and the morphological change of the cells stimulated by FSH were blocked by OCT4-specific small interfering RNA. Moreover, our results showed that OCT4 mediated the increase in invasive capacity induced by FSH in ovarian cancer cells. Taken together, our work reveals that OCT4 is an essential mediator in FSH-induced EMT and invasion in epithelial ovarian cancer and may act as a potential therapeutic target.
Department of Obstetrics and Gynecology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China.
Lei
L
Liu
Department of Obstetrics and Gynecology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China.
Jing
J
Zhang
Department of Obstetrics and Gynecology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China.
Chi
C
Fang
Department of Obstetrics and Gynecology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China.
Zhenbo
Z
Zhang
Department of Obstetrics and Gynecology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China.
Youji
Y
Feng
Department of Obstetrics and Gynecology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China. Electronic address: xixiaoweix66@126.com.
Xiaowei
X
Xi
D001483:Base Sequence; D000077216:Carcinoma, Ovarian Epithelial; D005640:Follicle Stimulating Hormone / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D011962:Receptors, FSH / Q000502:physiology
D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D034741:RNA, Small Interfering; D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone
EMT; ERK1/2; Epithelial ovarian cancer; FSH; Invasion; OCT4