title: CASZ1 is a novel promoter of metastasis in ovarian cancer.
abstract: Epithelial ovarian cancer (EOC) carries the highest mortality rate of all gynecologic malignancies. This high mortality rate is attributed to the fact that most cases of ovarian cancer are detected at late stages when metastases are already present. Through microarray analysis, we previously demonstrated that castor zinc finger 1 (CASZ1) is up-regulated in EOC cells. In contrast to its role in EOC, CASZ1 functions a tumor suppressor in neuroblastoma. Human CASZ1 is predominantly expressed in 2 alternatively spliced isoforms: CASZ1a and CASZ1b. In the present study, we investigated the role of CASZ1 in ovarian cancer cell migration and invasion and assessed the value of CASZ1 expression as a prognostic indicator of metastasis in human ovarian cancer. We used a lentivirus expressing CASZ1-shRNA and a plasmid expressing CASZ1 from a CMV promoter to knockdown and overexpress CASZ1, respectively, in the MCAS, RMUG-S, TOV21G, and A2780(CP70) ovarian cancer cell lines. mRNA expression levels in tumor tissues and cell lines were measured using quantitative real-time PCR, and CASZ1 protein expression in EOC and paired metastatic tumor tissues was analyzed using immunohistochemistry. We found that CASZ1 was highly expressed in EOC tissues and ovarian cancer cell lines and that CASZ1 knockdown suppressed cell migration and invasion in EOC cells. CASZ1a and CASZ1b exerted similar effects on cell migration and invasion in EOC cells. In addition, CASZ1 promoted the epithelial-mesenchymal transition in EOC cells, and CASZ1 knockdown suppressed cancer metastasis in vivo. Furthermore, CASZ1 protein levels were elevated in human metastatic ovarian tumor tissues. Together, these results indicate that CASZ1 is a novel promoter of EOC metastasis and is highly up-regulated in metastatic EOC tumors.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Tainan, Taiwan.
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Wu
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Tainan, Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Chang
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Tainan, Taiwan.
authors.forename: Yuan-Jhe
authors.initials: YJ
authors.lastname: Chuang
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University Tainan, Taiwan.
authors.forename: Jia-En
authors.initials: JE
authors.lastname: Wu
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University Tainan, Taiwan.
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Tung
authors.affiliation: Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University Tainan, Taiwan.
authors.forename: Yeong-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Institute of Oral Medicine, College of Medicine, National Cheng Kung University Tainan, Taiwan.
authors.forename: Yuh-Ling
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Tainan, Taiwan.
authors.forename: Tse-Ming
authors.initials: TM
authors.lastname: Hong
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityTainan, Taiwan; Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityTainan, Taiwan.
authors.forename: Keng-Fu
authors.initials: KF
authors.lastname: Hsu
keywords: CASZ1; cancer metastasis; epithelial ovarian cancer