Deldar Abad Paskeh, MahshidMirzaei, SepidehAshrafizadeh, MiladZarrabi, AliSethi, Gautam2021-12-062021-12-062021Deldar Abad Paskeh, M., Mirzaei, S., Ashrafizadeh, M., Zarrabi, A., & Sethi, G. (2021). Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways. Journal of hepatocellular carcinoma, 8, 1415–1444.https://doi.org/10.2147/JHC.S336858https://hdl.handle.net/20.500.12713/2303Liver 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/?-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 ?-catenin enhances expression level of genes such as c-Myc and MMPs in increasing cancer progression. The mutation of CTNNB1 gene encoding ?-catenin and its overexpression can lead to HCC progression. ?-catenin signaling enhances cancer stem cell features of HCC and promotes their growth rate. Furthermore, ?-catenin prevents apoptosis in HCC cells and increases their migration via triggering EMT and upregulating MMP levels. It is suggested that ?-catenin signaling participates in mediating drug resistance and immuno-resistance in HCC. Upstream mediators including ncRNAs can regulate ?-catenin signaling in HCC. Anti-cancer agents inhibit ?-catenin signaling and mediate its proteasomal degradation in HCC therapy. Furthermore, clinical studies have revealed the role of ?-catenin and its gene mutation (CTNBB1) in HCC progression. Based on these subjects, future experiments can focus on developing novel therapeutics targeting Wnt/?-catenin signaling in HCC therapy.eninfo:eu-repo/semantics/openAccessWnt SignalingDrug ResistanceImmunotherapyLiver CancerNon-coding RNAsReview Article81415144434858888WOS:000723700600001Q110.2147/JHC.S336858