title: Follicle-stimulating hormone induced epithelial-mesenchymal transition of epithelial ovarian cancer cells through follicle-stimulating hormone receptor PI3K/Akt-Snail signaling pathway.
abstract: OBJECTIVE
  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.
authors.affiliation: *Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University; †Department of Obstetrics and Gynecology, Shanghai First People's Hospital, Shanghai Jiaotong University; and ‡Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital,Shanghai Tongji University, Shanghai, People's Republic of China.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Yang
authors.forename: Jiawen
authors.initials: J
authors.lastname: Zhang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Youji
authors.initials: Y
authors.lastname: Feng
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018283:Cystadenocarcinoma, Papillary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005455:Fluorescent Antibody Technique; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011962:Receptors, FSH / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D006728:Hormones; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011962:Receptors, FSH; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D005640:Follicle Stimulating Hormone; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt