title: Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway.
abstract: Extensive exposure to estrogen is generally acknowledged as a risk factor for endometrial cancer. Given that the accumulation of adipocytes also contributes to the increased production of estrogen, in the present study, we evaluated the expression of the fat mass and obesity-associated (FTO) gene in endometrial tumor tissues and further explored the mechanism of how estrogen facilitates FTO nuclear localization and promotes endometrial cancer cell proliferation. Immunohistochemical (IHC) staining assay was used to detect the FTO expression in endometrial tumor samples. Western blotting was performed to investigate the mechanism of estrogen-induced FTO nuclear localization. siRNA was used to knock down ERα and further explore its role in FTO nuclear localization. MTT assay was carried out to determine cell proliferation. We found that FTO was overexpressed in endometrial carcinoma tissues and served as a poor prognostic marker. Additionally, estrogen induced FTO nuclear accumulation via the mTOR signaling pathway and the nuclear localization was ERα-dependent, which contributed to enhanced proliferative activity. Therefore, the present study provides new insight into the mechanisms of estrogen-induced proliferation, implying the possibility of using FTO as a potential therapeutic target for the treatment of endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200080, P.R. China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200080, P.R. China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200080, P.R. China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200080, P.R. China.
authors.forename: Youji
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases