Abstract 2857: S100A14 plays an important role in cell growth and metastasis of epithelial ovarian cancer through PI3K-AKT pathway

Abstract

Background: S100A14 is an EF-hand containing calcium protein of the S100 protein family that exerts its biological effects on different types of cancers. The roles of S100A14 in tumorigenesis and its underlying mechanism have not been fully understood. This study aims to investigate the clinical significance and possible mechanisms of action of S100A14 in the growth and metastasis of epithelial ovarian cancer (EOC). Method: S100A14 expression in ovarian cancer was studied using a total of 104 ovarian tissue specimens (13 normal ovarian tissues, 10 benign ovarian tumors, 10 borderline ovarian tumors, and 71 EOC tissues) via immunohistochemistry. We investigated the possible functions of S100A14 in EOC stable cell by lentivirus-mediated overexpression and short hairpin RNA (shRNA). Results: S100A14 protein was significantly over-expressed in EOC cells and tissues. S100A14 expression was significantly associated with advanced stage (P<0.001), serous type (P=0.004), and poor tumor grade (P<0.001). Patients with S100A14 overexpression had shorter overall (Hazard Ratio = 4.53 [1.16-17.69], P=0.029) and disease-free survival (Hazard Ratio = 3.10 [1.22-7.89], P=0.017) in multivariate analysis. In vitro analysis of cell function revealed that cell proliferation, migration and invasion were regulated by S100A14. We investigated the underlying mechanism and found that the phosphorylation levels of AKT have increased after S100A14 overexpression. Inhibition of AKT by a specific AKT inhibitor (MK-2206) and PI3K inhibitor (wortmannin) at least partly reversed the AKT-phosphorylation events in S100A14-overexpressed cells. Conclusions: The data revealed the aberrant expression of S100A14 in ovarian cancer, suggesting a potentially important role of S100A14 in ovarian carcinogenesis; S100A14 regulated AKT via phosphorylation of its ser473 site also implies that S100A14 could be used as a novel therapeutic target for ovarian cancer treatment. Citation Format: Hanbyoul Cho, Maria Lee, Ha-Yeon Shin, Wookyeom Yang, Eun-ju Lee, Hyunja Kwon, Sol Kim, Jae-Hoon Kim. S100A14 plays an important role in cell growth and metastasis of epithelial ovarian cancer through PI3K-AKT pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2857. doi:10.1158/1538-7445.AM2014-2857

Roles of metformin‐mediated girdin expression in metastasis of epithelial ovarian cancer

“…Prevention of AKT pathway restricted metastatic behavior of EOC cells (Cho et al, 2014). Since, Girdin is a substrate of AKT phosphorylation (Enomoto et al, 2005), and involved in metastatic regulation of hepatocellular carcinoma (HCC) in vitro (Wu et al, 2016).…”