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β-Catenin Activation in Hepatocellular Cancer: Implications in Biology and Therapy

Krutsenko, Yekaterina and Singhi, Aatur D. and Monga, Satdarshan P. (2021) β-Catenin Activation in Hepatocellular Cancer: Implications in Biology and Therapy. Cancers, 13 (8). p. 1830. ISSN 2072-6694

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Hepatocellular cancer (HCC), the most common primary liver tumor, has been gradually growing in incidence globally. The whole-genome and whole-exome sequencing of HCC has led to an improved understanding of the molecular drivers of this tumor type. Activation of the Wnt signaling pathway, mostly due to stabilizing missense mutations in its downstream effector β-catenin (encoded by CTNNB1) or loss-of-function mutations in AXIN1 (the gene which encodes for Axin-1, an essential protein for β-catenin degradation), are seen in a major subset of HCC. Because of the important role of β-catenin in liver pathobiology, its role in HCC has been extensively investigated. In fact, CTNNB1 mutations have been shown to have a trunk role. β-Catenin has been shown to play an important role in regulating tumor cell proliferation and survival and in tumor angiogenesis, due to a host of target genes regulated by the β-catenin transactivation of its transcriptional factor TCF. Proof-of-concept preclinical studies have shown β-catenin to be a highly relevant therapeutic target in CTNNB1-mutated HCCs. More recently, studies have revealed a unique role of β-catenin activation in regulating both tumor metabolism as well as the tumor immune microenvironment. Both these roles have notable implications for the development of novel therapies for HCC. Thus, β-catenin has a pertinent role in driving HCC development and maintenance of this tumor-type, and could be a highly relevant therapeutic target in a subset of HCC cases.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Krutsenko, Yekaterina
Singhi, Aatur D.ads130@pitt.eduads130
Monga, Satdarshan P.smonga@pitt.edusmonga
Date: 12 April 2021
Date Type: Publication
Journal or Publication Title: Cancers
Volume: 13
Number: 8
Publisher: MDPI AG
Page Range: p. 1830
DOI or Unique Handle: 10.3390/cancers13081830
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
Uncontrolled Keywords: β-catenin mutations, tumor metabolism, tumor immunology, molecular therapeutics, precision medicine
ISSN: 2072-6694
Official URL:
Funders: National Institutes of Health, Endowed Chair for Experimental Pathology, Clinical Biospecimen Repository and Processing Core of the Pittsburgh Liver Research Center
Article Type: Review
Date Deposited: 08 Jun 2021 17:28
Last Modified: 08 Jun 2021 17:28


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