Abstract C123: Loss of tumor suppressor NDRG2 promotes cell proliferation and migration/invasion of oral squamous cell carcinoma cells

Abstract

Abstract More than 90% of oral cancers are diagnosed as oral squamous cell carcinoma (OSCC). Although there has been much understanding of the molecular pathogenesis of OSCC, the majority of patients still die from local recurrence and metastasis of tumors. Recently, N-myc downstream-regulated gene 2 (NDRG2) has been known as a tumor suppressor gene in various types of malignancies, but its function and molecular mechanism in OSCC are very little known. To verify the functional roles of NDRG2 in OSCC, we screened six OSCC cell lines first using western blotting. Among the 6 cell lines, HN22 cell line showing high expression of NDRG2 was selected and treated with anti-NDRG2 small interfering RNA (siRNA). The effect of NDRG2 on cell proliferation was evaluated at 24h, 48h, and 72h after treatment of 50nM of anti-NDRG2 siRNA. In addition, in vitro migration and invasion assays were performed after same treatment. Western blot analysis showed variable levels of NDRG2 in 6 OSCC cell lines. Normal human oral keratinocyte as a positive control expressed very high level of NDRG2. Among 6 OSCC cell lines, three cell lines had very low level or absence of NDRG2, but remaining three cell lines including HN22 cell had moderate to high level of NDRG2. After 24h treatment of anti-NDRG2 siRNA on the HN22 cells, NDRG2 expression was significantly downregulated. In cell proliferation assay after treatment of 50nM of anti-NDRG2 siRNA, there was a significant increase in cell growth of HN22 cells when compared with the control (p=.005). In wound healing assay, NDRG2-downregulated HN22 cell line showed much more closure of wound area when compared with the control (p=.007). From the invasion assay after treatment, there was a significant increase in invasion ability of HN22 cells (p<.001). These date indicate that loss of function of NDRG2 as a tumor suppressor can enhance the cell growth, migration, and invasion of OSCC cells. Our results suggest that loss of NDRG2 expression plays a role in tumor progression of OSCC by enhancing tumor cell growth, motility, and invasiveness. Therefore, recovering loss of function of NDRG2 may be a new therapeutic strategy for OSCC treatment. Citation Format: Hye-Jung Yoon, Chi-Hyun Ahn, Ji-Hoon Kim. Loss of tumor suppressor NDRG2 promotes cell proliferation and migration/invasion of oral squamous cell carcinoma cells [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C123. doi:10.1158/1535-7163.TARG-19-C123