title: Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK-ERK pathway.
abstract: Mortalin is frequently overexpressed in human malignancies. Previous studies have suggested that mortalin contributes to ovarian cancer development and progression, but further investigation is warranted. The aim of this study is to elucidate the mechanism of mortalin in ovarian cancer development and progression. In this study, lentivirus-delivered mortalin short hairpin RNA (shRNA) was used to knockdown mortalin expression in A2780 and A2780/cis ovarian cancer cell lines, and lentiviral mortalin-pLVX-AcGFP was used to generate mortalin-overexpressing cell lines. The results demonstrated that decreased mortalin expression reduced ovarian cancer cell proliferation, colony formation, migration and invasion by Cell Counting Kit-8 assay, colony formation assay, wounding healing assay and Transwell cell invasion assay, respectively. Flow cytometry results suggested that mortalin promotes the G1 transition, leading to faster restoration of a normal cell-cycle distribution. Cell-cycle proteins, including C-myc and Cyclin-D1, significantly increased, and Cyclin-B1 remarkably decreased upon mortalin down-regulation. Western blot analysis showed that mortalin knockdown significantly decreased p-c-Raf and phospho-extracellular-regulated protein kinases (p-ERK1/2) pathways but not the Jun N-terminal kinase pathway, whereas mortalin overexpression had the opposite effect. Taken together, these results indicate that mortalin is an oncogenic factor, and mitogen-activated protein kinase-ERK signalling pathway activation by mortalin may contribute to ovarian cancer development and progression.
authors.affiliation: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China. liuwen@shmu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China. jzuo@shmu.edu.cn.
authors.forename: Ji
authors.initials: J
authors.lastname: Zuo
mesh_terms: D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D009857:Oncogenes; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018840:HSP70 Heat-Shock Proteins; C080352:mortalin; D019938:Cyclin D1
keywords: MAPK-ERK; mortalin; ovarian cancer development and progression