title: ADP-ribosylation factor-like 4C (ARL4C), a novel ovarian cancer metastasis suppressor, identified by integrated genomics.
abstract: Understanding the molecular mechanisms involving the initiation, progression, and metastasis of ovarian cancer is important for the prevention, detection, and treatment of ovarian cancer. In this study, two ovarian cancer cell lines, HO-8910 and its derivative HO-8910PM with highly metastatic potential, were applied to comparative genomic hybridization (CGH) analysis. We found 14 chromosome fragments with different copy numbers between the two cell lines, one (2q36.1-37.3) of which was confirmed to be one-copy loss in HO-8910PM by fluorescent in situ hybridization (FISH). Using the microarray data on gene expression profiles from these cell lines, 6 significantly expression-decreased genes located on 2q36.1-37.3 in HO-8910PM were identified. Of the 6 genes, ARL4C was identified as a novel ovarian cancer-related gene using integrated molecular and genomic analyses. ARL4C mRNA expression was validated by quantitative PCR to be markedly decreased in HO-8910PM cells, compared to that in HO-8910. Both overexpression and knockdown of ARL4C demonstrated that low ARL4C expression promotes the migration but not influences proliferation capability of ovarian cancer cells in vitro, indicating its specific role in ovarian cancer progression. Furthermore, ovarian cancer patients with medium and high expression of ARL4C mRNA had a favorable prognosis compared to those with low expression, suggesting the ARL4C could be a potential predictor for ovarian cancer prognosis.
authors.affiliation: Cancer Research Institute, Zhejiang Cancer Hospital Hangzhou 310022, Zhejiang, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.affiliation: Gynecologic Oncology and Breast Cancer Unit, S. Anna Hospital Turin 10100, Italy.
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.affiliation: Cancer Research Institute, Zhejiang Cancer Hospital Hangzhou 310022, Zhejiang, China.
authors.forename: Shenhua
authors.initials: S
authors.lastname: Xu
authors.affiliation: Cancer Research Institute, Zhejiang Cancer Hospital Hangzhou 310022, Zhejiang, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Cancer Research Institute, Zhejiang Cancer Hospital Hangzhou 310022, Zhejiang, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Obstetrics and Gynecology and Breast Cancer Unit, Mauriziano Hospital, University of Turin Torino 10100, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Biglia
authors.affiliation: Cancer Research Institute, Zhejiang Cancer Hospital Hangzhou 310022, Zhejiang, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Feng
authors.affiliation: Cancer Research Institute, Zhejiang Cancer Hospital Hangzhou 310022, Zhejiang, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Ying
authors.affiliation: Cancer Research Institute, Zhejiang Cancer Hospital Hangzhou 310022, Zhejiang, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Gynaecology and Obstetrics, University of Turin Turin 10100, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Benedetto
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center Hawaii 96813, USA.
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
keywords: ARL4C; Ovarian cancer; genomics; metastasis; prognosis; tumor cell biology