CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling.

Abstract

CD146 plays a key role in cancer progression and metastasis. Cancer stem cells (CSCs) are responsible for tumor initiation, drug resistance, metastasis, and recurrence. In this study, we explored the role of CD146 in the regulation of liver CSCs. Here, we demonstrated that CD146 was highly expressed in liver CSCs. CD146 overexpression promoted the self-renewal ability and chemoresistance of Hepatocellular Carcinoma (HCC) cells in vitro and tumorigenicity in vivo. Inversely, knockdown of CD146 restrained these abilities. Mechanistically, CD146 activated the NF-κB signaling to up-regulate JAG2 expression and activated the Notch signaling, which resulted in increased stemness of HCC. Furthermore, JAG2 overexpression restored the Notch signaling activity, the stemness, and chemotherapeutic resistance caused by CD146 knockdown. These results demonstrated that CD146 positively regulates HCC stemness by activating the JAG2-NOTCH signaling. Combined targeting of CD146 and JAG2 may represent a novel therapeutic strategy for HCC treatment.