β-Catenin signaling in hepatocellular carcinoma

• Published in: The Journal of clinical investigation Vol. 132; no. 4; pp. 1 - 10
• Main Authors: Xu, Chuanrui, Xu, Zhong, Zhang, Yi, Evert, Matthias, Calvisi, Diego F, Chen, Xin
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 15.02.2022
• Subjects: Axin Protein - genetics; Axin Protein - metabolism; beta Catenin - genetics; beta Catenin - metabolism; Biomedical research; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Gene expression; Genomic analysis; Hepatocellular carcinoma; Humans; Kinases; Ligands; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Medical prognosis; Mutation; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Phosphorylation; Proteins; Response rates; Review; Signal transduction; Tumors; Wnt protein; Wnt Signaling Pathway; β-Catenin
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/JCI154515

Deregulated Wnt/β-catenin signaling is one of the main genetic alterations in human hepatocellular carcinoma (HCC). Comprehensive genomic analyses have revealed that gain-of-function mutation of CTNNB1, which encodes β-catenin, and loss-of-function mutation of AXIN1 occur in approximately 35% of human HCC samples. Human HCCs with activation of the Wnt/β-catenin pathway demonstrate unique gene expression patterns and pathological features. Activated Wnt/β-catenin synergizes with multiple signaling cascades to drive HCC formation, and it functions through its downstream effectors. Therefore, strategies targeting Wnt/β-catenin have been pursued as possible therapeutics against HCC. Here, we review the genetic alterations and oncogenic roles of aberrant Wnt/β-catenin signaling during hepatocarcinogenesis. In addition, we discuss the implication of this pathway in HCC diagnosis, classification, and personalized treatment.