CD24 promotes HCC progression via triggering Notch-related EMT and modulation of tumor microenvironment.

CD24 is known as a cell surface molecule in hematopoiesis and also described as a diagnostic marker for tumors. Previous studies suggested the important role of CD24 in hepatocellular carcinoma (HCC) pathogenesis. However, precise functions of CD24 in HCC are still unknown. Here, we found that CD24 is highly expressed in HCC both in mRNA and protein levels. Further, the epithelial-mesenchymal transition (EMT) and Notch1 signaling activations mediated by CD24 were elucidated as potential mechanisms of HCC promotion in Hepa1-6/Hepa1-6-CD24 cell models. Additionally, possible systemic immune reaction was explored through immune cells and Hepa1-6/Hepa1-6-CD24 cell co-culture. We demonstrated that the EMT process of HCC cell was effectively induced by CD24; also, the tumor immune microenvironment was changed by facilitating Notch-related EMT in vivo. These results reveal the underlying link between the HCC processes mediated by CD24. Moreover, as a clear tumor promoter, CD24 is considered a potential new target for HCC treatment.