Sox13 promotes hepatocellular carcinoma metastasis by transcriptionally activating Twist1

Abstract

SRY (sex-determining region Y)-box 13 (Sox13), a member of group D of the SRY-related high mobility group (HMG) box (Sox) family, is a critical regulator of embryonic development and cartilage formation. Few studies have investigated the role of Sox13 in tumorigenesis. The present study reveals the clinical significance and biological function of Sox13 in hepatocellular carcinoma (HCC). First, the expression of Sox13 in HCC samples was evaluated by qRT-PCR and western blotting, and its association with clinicopathological features and prognosis was determined. We found that Sox13 expression was higher in tumor tissue than in paired nontumor tissue. The upregulation of Sox13 was associated with poor differentiation, metastasis, recurrence and poor overall, and tumor-free survival of HCC patients. The function of Sox13 on HCC cell migration and invasion was then assessed by Transwell assay, and the results demonstrated that Sox13 promoted HCC cell invasion, migration, and epithelial-to-mesenchymal transition (EMT). Notably, the invasion, migration, and EMT of HCC cells induced by Sox13 overexpression could be abolished by Twist1 depletion, and Sox13 was positively correlated with Twist1 at both the mRNA and protein levels. Mechanistically, we revealed that Sox13 activated Twist1 transcription and consequently upregulated Twist1 expression. Furthermore, Sox13 formed a heterodimer with Sox5, and this heterodimer functionally cooperated to enhance the transcriptional activity of Twist1. Our findings suggest that Sox13 serves as an oncogene in HCC, and might be a novel prognostic and therapeutic candidate.