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

• Published in: Journal of hepatocellular carcinoma Vol. 8; pp. 1415 - 1444
• Main Authors: Deldar Abad Paskeh, Mahshid, Mirzaei, Sepideh, Ashrafizadeh, Milad, Zarrabi, Ali, Sethi, Gautam
• Format: Journal Article
• Language: English
• Published: New Zealand Taylor & Francis Ltd 01.01.2021; Dove
• Subjects: Antitumor agents; Apoptosis; Binding sites; c-Myc protein; Cancer therapies; Cell migration; Chemotherapy; CTNNB1 gene; Cytotoxicity; Developing countries; Drug resistance; Epigenetics; Growth rate; Hepatitis B; Hepatocellular carcinoma; Kinases; LDCs; Ligands; Liver cancer; Medical prognosis; Metastasis; MicroRNAs; Mutation; Myc protein; Nuclear transport; Phosphorylation; Point mutation; Proteasomes; Proteins; Review; Signal transduction; Stem cells; Tumor necrosis factor-TNF; Tumors; Wnt protein; β-Catenin; Wnt signaling; liver cancer; drug resistance; non-coding RNAs; immunotherapy
• ISSN: 2253-5969; 2253-5969
• DOI: 10.2147/JHC.S336858

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/β-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 β-catenin enhances expression level of genes such as c-Myc and MMPs in increasing cancer progression. The mutation of gene encoding β-catenin and its overexpression can lead to HCC progression. β-catenin signaling enhances cancer stem cell features of HCC and promotes their growth rate. Furthermore, β-catenin prevents apoptosis in HCC cells and increases their migration via triggering EMT and upregulating MMP levels. It is suggested that β-catenin signaling participates in mediating drug resistance and immuno-resistance in HCC. Upstream mediators including ncRNAs can regulate β-catenin signaling in HCC. Anti-cancer agents inhibit β-catenin signaling and mediate its proteasomal degradation in HCC therapy. Furthermore, clinical studies have revealed the role of β-catenin and its gene mutation ( ) in HCC progression. Based on these subjects, future experiments can focus on developing novel therapeutics targeting Wnt/β-catenin signaling in HCC therapy.