The Oncogenic role of CD133 in Hepatocellular Carcinoma

Abstract

Liver cancer (hepatocellular carcinoma, HCC) is one of the most prevalent malignancies worldwide. Because of the late diagnosis of the disease, the prognosis of HCC patient is often undesirable. Cancer Stem Cell (CSC), which represents a subpopulation of cancer cells with stem-like properties, plays a critical role in tumorigenesis and contributes significantly to the relapse and chemo-drug resistance of cancers. The cell surface marker, CD133/Prominin-1, has been identified as a biomarker for CSC in various cancers, including HCC. To understand the role of CD133 in hepatocarcinogenesis, we expressed CD133 in HCC cells and showed that CD133 significantly promoted cell growth. Interestingly, our data also indicated that expression of CD133 led to chromosomal instability indicated by elevation of aneuploidy population and centrosome numbers in CD133 expressing cells. To understand the molecular mechanism, we observed that a putative tumour suppressor in HCC, called TAX1-binding protein 2 (TAX1BP2), which functions as a centrosome over-duplication suppresser, was downregulated by CD133. Taken together, these data suggest that CD133 plays an oncogenic role in HCC and may downregulate TAX1BP2 to promote chromosome instability, centrosome duplication and hepatocarcinogenesis.