Wnt/?-Catenin signaling as a driver of hepatocellular carcinoma progression: an emphasis on molecular pathways

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Küçük Resim

Tarih

2021

Dergi Başlığı

Dergi ISSN

Cilt Başlığı

Yayıncı

Dove Medical Press

Erişim Hakkı

info:eu-repo/semantics/openAccess

Özet

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/?-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.

Açıklama

Anahtar Kelimeler

Wnt Signaling, Drug Resistance, Immunotherapy, Liver Cancer, Non-coding RNAs

Kaynak

Journal of Hepatocellular Carcinoma

WoS Q Değeri

Q1

Scopus Q Değeri

Cilt

8

Sayı

Künye

Deldar 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.