title: SERPINA3 promotes endometrial cancer cells growth by regulating G2/M cell cycle checkpoint and apoptosis.
abstract: Endometrial carcinoma (EC) is the most common gynecologic cancer worldwide and is one of the leading causes of death in women. Therefore, it is urgent to elucidate the pathological mechanisms of EC. SERPINA3 is a member of the serpin super-family of protease inhibitors. Its aberrant expression has been observed in various tumor cells. However, its clinical significance and biological function in endometrial cancer remains unknown. In the present study, we demonstrated that SERPINA3 expression was significantly up-regulated in EC samples and was closely correlated with lower differentiation, higher stage, positive lymph node or vascular thrombosis and negative estrogen receptor (ER), indicating a poor prognosis. We then demonstrated that SERPINA3 promoted EC cells proliferation by regulating G2/M checkpoint in cell cycle and inhibited cells apoptosis, and we further uncovered that the pro-proliferative effect of SERPINA3 on EC was likely ascribed to the activation of MAPK/ERK1/2 and PI3K/AKT signaling. The results of our study may provide insight into the application of SERPINA3 as a novel predictor of clinical outcomes and a potential therapeutic target of EC.
authors.affiliation: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University 201499 Shanghai, P.R. China.
authors.forename: Guang-Dong
authors.initials: GD
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine 200240 Shanghai, P.R. China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University 201499 Shanghai, P.R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Obstetrics and Gynecology, Changzhou Maternal and Child Care Hospital Changzhou, 213003, Jiangsu, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine 200240 Shanghai, P.R. China.
authors.forename: Ming-Ze
authors.initials: MZ
authors.lastname: Ma
authors.affiliation: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University 201499 Shanghai, P.R. China.
authors.forename: Lin-Yan
authors.initials: LY
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University 201499 Shanghai, P.R. China.
authors.forename: Jing-Hao
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University 201499 Shanghai, P.R. China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Song
authors.affiliation: Fudan University Shanghai Cancer Center 200032 Shanghai, P.R. China.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University 201499 Shanghai, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine 200240 Shanghai, P.R. China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D016889:Endometrial Neoplasms / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D059566:M Phase Cell Cycle Checkpoints / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015843:Serpins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: C516148:SERPINA3 protein, human; D015843:Serpins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: G2/M checkpoint; SERPINA3; apoptosis; endometrial cancer; proliferation