Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 May;60(5):466-481.
doi: 10.1007/s11626-024-00858-7. Epub 2024 Feb 20.

Wnt/β-catenin signaling pathway in liver biology and tumorigenesis

Affiliations
Review

Wnt/β-catenin signaling pathway in liver biology and tumorigenesis

Shinji Matsumoto et al. In Vitro Cell Dev Biol Anim. 2024 May.

Abstract

The Wnt/β-catenin pathway is an evolutionarily conserved signaling pathway that controls fundamental physiological and pathological processes by regulating cell proliferation and differentiation. The Wnt/β-catenin pathway enables liver homeostasis by inducing differentiation and contributes to liver-specific features such as metabolic zonation and regeneration. In contrast, abnormalities in the Wnt/β-catenin pathway promote the development and progression of hepatocellular carcinoma (HCC). Similarly, hepatoblastoma, the most common childhood liver cancer, is frequently associated with β-catenin mutations, which activate Wnt/β-catenin signaling. HCCs with activation of the Wnt/β-catenin pathway have unique gene expression patterns and pathological and clinical features. Accordingly, they are highly differentiated with retaining hepatocyte-like characteristics and tumorigenic. Activation of the Wnt/β-catenin pathway in HCC also alters the state of immune cells, causing "immune evasion" with inducing resistance to immune checkpoint inhibitors, which have recently become widely used to treat HCC. Activated Wnt/β-catenin signaling exhibits these phenomena in liver tumorigenesis through the expression of downstream target genes, and the molecular basis is still poorly understood. In this review, we describe the physiological roles of Wnt/b-catenin signaling and then discuss their characteristic changes by the abnormal activation of Wnt/b-catenin signaling. Clarification of the mechanism would contribute to the development of therapeutic agents in the future.

Keywords: GREB1; HNF4α; Hepatoblastoma; Hepatocellular carcinoma; Wnt; β-Catenin.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Abitbol S, Dahmani R, Coulouarn C, Ragazzon B, Mlecnik B, Senni N, Savall M, Bossard P, Sohier P, Drouet V, Tournier E, Dumont F, Sanson R, Calderaro J, Zucman-Rossi J, Vasseur-Cognet M, Just PA, Terris B, Perret C, Gilgenkrantz H (2018) AXIN deficiency in human and mouse hepatocytes induces hepatocellular carcinoma in the absence of β-catenin activation. J Hepatol 68:1203–1213 - PubMed
    1. Adebayo Michael AO, Ko S, Tao J, Moghe A, Yang H, Xu M, Russell JO, Pradhan-Sundd T, Liu S, Singh S, Poddar M, Monga JS, Liu P, Oertel M, Ranganathan S, Singhi A, Rebouissou S, Zucman-Rossi J, Ribback S, Calvisi D, Qvartskhava N, Görg B, Häussinger D, Chen X, Monga SP (2019) Inhibiting Glutamine-Dependent mTORC1 Activation Ameliorates Liver Cancers Driven by β-Catenin Mutations. Cell Metab 29:1135-1150.e1136 - PubMed
    1. Apte U, Zeng G, Muller P, Tan X, Micsenyi A, Cieply B, Dai C, Liu Y, Kaestner KH, Monga SP (2006) Activation of Wnt/β-catenin pathway during hepatocyte growth factor-induced hepatomegaly in mice. Hepatology 44:992–1002 - PubMed
    1. Armengol C, Cairo S, Fabre M, Buendia MA (2011) Wnt signaling and hepatocarcinogenesis: the hepatoblastoma model. Int J Biochem Cell Biol 43:265–270 - PubMed
    1. Behari J, Yeh TH, Krauland L, Otruba W, Cieply B, Hauth B, Apte U, Wu T, Evans R, Monga SP (2010) Liver-specific β-catenin knockout mice exhibit defective bile acid and cholesterol homeostasis and increased susceptibility to diet-induced steatohepatitis. Am J Pathol 176:744–753 - PubMed - PMC

LinkOut - more resources