title: Forkhead transcription factor 1 inhibits endometrial cancer cell proliferation via sterol regulatory element-binding protein 1.
abstract: The morbidity and mortality associated with endometrial cancer (EC) has increased in recent years. Regarded as a tumor suppressor, forkhead transcription factor 1 (FOXO1) has various biological activities and participates in cell cycle progression, apoptosis and differentiation. Notably, FOXO1 also functions in the regulation of lipogenesis and energy metabolism. Lipogenesis is a feature of cancer and is upregulated in EC. Sterol regulatory element-binding protein 1 (SREBP1) is a transcription factor that is also able to regulate lipogenesis. Increased expression of SREBP1 is directly correlated with malignant transformation of tumors. A previous study demonstrated that SREBP1 was highly expressed in EC and directly resulted in tumorigenesis. However, the association between FOXO1 and SREBP1 in EC is not clear. In the present study, lentiviruses overexpressing FOXO1 were used in cell transfection and transduction. Cell viability assays demonstrated that the overexpression of FOXO1 was able to suppress cell proliferation significantly in Ishikawa and AN3 CA cell lines. In addition, FOXO1 overexpression significantly inhibited cell migration and invasion abilityin vitro. In xenograft models, overexpression of FOXO1 suppressed cell tumorigenesis, and western blot analysis demonstrated that SREBP1 expression was markedly reduced in the FOXO1-overexpressing cells. It may therefore be concluded that FOXO1 is able to inhibit the proliferative capacity of cellsin vitroandin vivo, in addition to the migratory and invasive capacitiesin vitroby directly targeting SREBP1.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China; Department of Obstetrics and Gynecology, Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, P.R. China.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ultrasonography, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Hengzi
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutical Chemistry, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250012, P.R. China.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Che
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
keywords: endometrial cancer; forkhead transcription factor 1; sterol regulatory element-binding protein 1