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.