Overexpression of CD133 promotes tumourigenicity and suppresses TAX1PB2 in hepatocellular carcinoma

Abstract

CD133 is a transmembrane protein that has been identified as a marker for cancer stem cells (CSCs) in liver cancer (hepatocellular carcinoma, HCC). CD133-positive HCC CSCs are more proliferative, tumorigenic and chemoresistant than its counterparts, for which the mechanism remains unclear. To elucidate the function of CD133, we have established inducible stable expression cell lines for CD133. The stable expression of CD133 in these stable expression clones were confirmed using western blotting and the flow cytometry analyses. Furthermore, colony formation assay was performed and the result showed that overexpression of CD133 significantly increased the tumorigenicity of HCC cell line, SMMC-7721. More interestingly, we found that CD133 was a negative regulator of a tumor suppressor protein Tax1 binding protein 2 (TAX1BP2), which is previously identified as an intrinsic block of centrosome overduplication. The expression of TAX1BP2 at both protein and transcript levels was downregulated in sorted CD133-positive cells. As revealed by luciferase reporter assay, the expression of CD133 could significantly suppressed the promoter activity of TAX1BP2, suggesting that CD133 is a suppressor of TAX1BP2 expression. Taken together, our work suggests that CD133 may contribute to tumorigenicity via suppression of TAX1BP2 expression.