Abstract 1720: Role of SENP1 in HBx-induced cell migration and stemness-related properties in hepatocellular carcinoma

Abstract

Abstract Hepatocellular carcinoma (HCC) is the sixth most common cancer, and the third leading cause of cancer mortality worldwide. Surgical resection can be curative for early stage HCC, but the risk of tumor recurrence remains high. Tumor stemness properties have been linked to early recurrence of HBV-related HCC (HBV-HCC), which continues to be a great challenge in clinical practice. However, the progress in the strategy of individualized therapy against HBV-HCC is slow and disappointed. Here we demonstrate that HBx regulates the cell migration and cancer stemness properties of HCC cells through Sentrin-specific protease 1 (SENP1) modification. By a large cohort of HCC patients receiving curative heptectomy, we found that SENP1 expression level is highly associated with the gene expression levels of cell migration-related gene SNAIL/TWIST and pluripotency-related gene OCT4 particularly in HBV-HCC. Furthermore, SENP1 expression level is significantly associated with tumor metastasis as well as the early recurrence of HCC using Kaplan-Meier analysis. Further experiments using cell line model, we demonstrated that HBx overexpression not only increases the protein levels of SENP1 and pluripotent transcription factor OCT4, but also enhances cell migration in HepG2 cells. Inhibition of SENP1 significantly suppressed the HBx-induced cell migration and cancer stemness in vitro and in vivo. In summary, in this work, we demonstrate that SENP1 plays a critical role in HBx-induced cell migration- and cancer stemness-related properties in HBV-HCC. Findings in this study will facilitate the potential strategy targeting on SENP1 for individualized adjuvant therapy against HBV-HCC. Citation Format: Te Sheng Chang, Yen-Hua Huang. Role of SENP1 in HBx-induced cell migration and stemness-related properties in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1720.