Abstract 1655: Targeting RFX-1 as a novel therapeutic strategy in hepatocellular carcinoma

Abstract

Abstract Regulatory factor X (RFX) 1 is a transcription factor that has been linked to negative regulation of tumor progression; however, its biological function and signaling cascades are unknown. In this study, we identify RFX-1 is a negative regulator of cell proliferation in human HCC. We demonstrated that ectopic expression of RFX-1 suppressed the colony forming ability of HCC cell lines through activating SHP-1 expression. In addition, nude mice bearing RFX-1-overexpressing tumors showed a repression of growth rate compared to the control group. Notably, we demonstrated that mRNA and protein level of RFX-1 is highly correlated with SHP-1 in 101 clinical HCC patients, indicating that RFX-1 might be a tumor suppressor of human HCC. To identify the RFX-1 activator for HCC therapy, we screened in-house small molecule library and found that one of small molecules, SC-2001, targeted RFX-1 and exhibited potent anti-tumor effect on HCC cells. In addition, we proved that SHP-1 activation and STAT3 dephosphorylation induced by SC-2001-activated RFX-1. Furthermore, genetic knockdown of RFX-1 reversed SC-2001-induced cell growth inhibition. Importantly, by a mouse xenograft model, silencing of RFX-1 could rescue the anti-HCC tumor effect caused by SC-2001 in vivo, implying that RFX-1 is a promising target for HCC therapy. Taken together, our results indicated that RFX-1/SHP-1/STAT3 signaling might a potential strategy for HCC therapy, and SC-2001 is a promising lead compound for drug development of HCC target therapy. Citation Format: Jung-Chen Su. Targeting RFX-1 as a novel therapeutic strategy in hepatocellular carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1655. doi:10.1158/1538-7445.AM2015-1655