Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

Liver cancers cause a high rate of death worldwide and hepatocellular carcinoma (HCC) is considered as the most common primary liver cancer. HCC remains a challenging disease to treat. Wnt/beta-catenin signaling pathway is considered a tumor-promoting factor in various cancers; hence, the present review focused on the role of Wnt signaling in HCC, and its association with progression and therapy response based on pre-clinical and clinical evidence. The nuclear translocation of beta-catenin enhances expression level of genes such as c-Myc and MMPs in increasing cancer progression. The mutation of CTNNB1 gene encoding beta-catenin and its overexpression can lead to HCC progression. beta-catenin signaling enhances cancer stem cell features of HCC and promotes their growth rate. Furthermore, beta catenin prevents apoptosis in HCC cells and increases their migration via triggering EMT and upregulating MMP levels. It is suggested that beta-catenin signaling participates in mediating drug resistance and immuno-resistance in HCC. Upstream mediators including ncRNAs can regulate beta-catenin signaling in HCC. Anti-cancer agents inhibit beta-catenin signaling and mediate its proteasomal degradation in HCC therapy. Furthermore, clinical studies have revealed the role of beta-catenin and its gene mutation (CTNBB1) in HCC progression. Based on these subjects, future experiments can focus on developing novel therapeutics targeting Wnt/beta-catenin signaling in HCC therapy.

Automated summary

This review discusses the role of Wnt signaling in hepatocellular carcinoma (HCC), including its promotion of HCC progression, impact on therapy response, and regulation of drug resistance and immune resistance mechanisms. Research shows that beta-catenin signaling in HCC cells can enhance cancer stem cell features, promote growth, and inhibit apoptosis, thus accelerating cancer development.