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At present, ovarian epithelial cancer is the leading killer among all gynecological malignancies.Despite much research, development of ovarian epithelial cancer is still not fully understood.Recent studies suggest that high Follicle-stimulating hormone (FSH) levels play a major role in ovarian epithelial carcinogenesis.Our in vitro and in vivo assays demonstrate that FSH can stimulate the proliferation and invasion of ovarian cancer cells, inhibit apoptosis, and facilitate neovascularization by increasing vascular endothelial growth factor (VEGF) expression.We have further shown that FSH stimulation enhances the expression of transient receptor potential channel C3 (TRPC3) at both the mRNA and protein levels.SiRNA-mediated silencing of TRPC3 expression inhibited the ability of FSH to stimulate proliferation and block apoptosis in ovarian cancer cell lines.FSH stimulation was associated with the translocation of TRPC3 from the cytoplasm to cell membrane,while also facilitating the influx of Ca2+ after treatment with a TRPC specific agonist.Knocking down TRPC3 abrogated Akt/PKB phosphorylation by FSH stimulation, leading to decreased expression of downstream effectors including survivin, HIF1α and VEGF.We also found that FSH stimulation could increase the expression of several stem cell markers, such as: Notch, Sox2, Nanog and OCT4, and induce the expansion of CD44+CD117+ immunophenotype cells, suggesting that FSH may involved in ovarian cancer-stem cell signaling pathways.In summary, FSH undoubtedly activates different signal transduction pathways.Understanding the role of FSH in ovarian cancer carcinogenesis will help to find a new way to treat and prevent ovarian cancer.