Purpose It has previously been shown that follicle-stimulating hormone (FSH) and its receptor contribute to epithelial ovarian cancer (EOC) development. Epithelial-mesenchymal transition (EMT) is the early event of metastasis in cancer. Therefore, the aim of this study was to investigate the roles of FSH and the FSH receptor (FSHR) in EMT of EOC.
Methods Ovarian cancer cells treated with various doses of FSH were used to investigate the effect of FSH on EMT. Small interfering RNA–mediated FSHR depletion or reexpression of FSHR by acute transfecting pcDNA-hFSHR plasmid was performed to determine the role of FSHR in FSH-induced EMT. Moreover, LY294002, a potent and specific cell-permeable inhibitor of phosphatidylinositol 3-kinases (PI3K), was selected to pretreat ovarian cancer cells to confirm whether PI3K/Akt signaling is involved in this event.
Results In the current study, FSH was found to induce the phenotypes of EMT including migration and invasion in EOC cells. Elevated FSHR levels promoted EMT, migration, and invasion, whereas small interfering RNA–mediated FSHR knockdown inhibited these processes. Moreover, the inhibition of FSH-induced PI3K/Akt signaling pathway attenuated Snail expression and the EMT process.
Conclusions Collectively, the findings of the current study indicate that FSH induced the EMT of ovarian cancer cells through the FSHR-PI3K/Akt-Snail signaling pathway.
- Follicle-stimulating hormone
- FSH receptor
- Epithelial ovarian cancer
- Epithelial-mesenchymal transition
- Phosphatidylinositol 3-kinase
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Yongbin Yang and Jiawen Zhang contributed equally to this study.
Supported by grants from the National Natural Science Foundation of China (NSFC No. 81020108027) and, in part, by grants (no. 10JC1413100) from the Shanghai Science and Technologic Committee.
The authors declare no conflicts of interest.
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