» Articles » PMID: 29125798

Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology

Overview
Journal Annu Rev Pathol
Publisher Annual Reviews
Specialty Pathology
Date 2017 Nov 11
PMID 29125798
Citations 199
Authors
Affiliations
Soon will be listed here.
Abstract

The liver is an organ that performs a multitude of functions, and its health is pertinent and indispensable to survival. Thus, the cellular and molecular machinery driving hepatic functions is of utmost relevance. The Wnt signaling pathway is one such signaling cascade that enables hepatic homeostasis and contributes to unique hepatic attributes such as metabolic zonation and regeneration. The Wnt/β-catenin pathway plays a role in almost every facet of liver biology. Furthermore, its aberrant activation is also a hallmark of various hepatic pathologies. In addition to its signaling function, β-catenin also plays a role at adherens junctions. Wnt/β-catenin signaling also influences the function of many different cell types. Due to this myriad of functions, Wnt/β-catenin signaling is complex, context-dependent, and highly regulated. In this review, we discuss the Wnt/β-catenin signaling pathway, its role in cell-cell adhesion and liver function, and the cell type-specific roles of Wnt/β-catenin signaling as it relates to liver physiology and pathobiology.

Citing Articles

Hepatic stellate cells control liver zonation, size and functions via R-spondin 3.

Sugimoto A, Saito Y, Wang G, Sun Q, Yin C, Lee K Nature. 2025; .

PMID: 40074890 DOI: 10.1038/s41586-025-08677-w.


Apolipoprotein E: A Potential Prognostic and Diagnostic Biomarker for Hepatocellular Carcinoma.

Li Y, Lu R, Abuduhailili X, Feng Y J Hepatocell Carcinoma. 2025; 12:301-324.

PMID: 39991517 PMC: 11844312. DOI: 10.2147/JHC.S504078.


Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.

Ma X, Huang T, Chen X, Li Q, Liao M, Fu L Signal Transduct Target Ther. 2025; 10(1):63.

PMID: 39920130 PMC: 11806117. DOI: 10.1038/s41392-024-02104-8.


Advances and challenges in molecular understanding, early detection, and targeted treatment of liver cancer.

Shi J, Zhu X, Yang J World J Hepatol. 2025; 17(1):102273.

PMID: 39871899 PMC: 11736488. DOI: 10.4254/wjh.v17.i1.102273.


Rspo3-mediated metabolic liver zonation regulates systemic glucose metabolism and body mass in mice.

Uno K, Uchino T, Suzuki T, Sayama Y, Edo N, Uno-Eder K PLoS Biol. 2025; 23(1):e3002955.

PMID: 39854351 PMC: 11759367. DOI: 10.1371/journal.pbio.3002955.


References
1.
Kinoshita M, Uchida T, Sato A, Nakashima M, Nakashima H, Shono S . Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice. J Hepatol. 2010; 53(5):903-10. DOI: 10.1016/j.jhep.2010.04.037. View

2.
Yang J, Cusimano A, Monga J, Preziosi M, Pullara F, Calero G . WNT5A inhibits hepatocyte proliferation and concludes β-catenin signaling in liver regeneration. Am J Pathol. 2015; 185(8):2194-205. PMC: 4530131. DOI: 10.1016/j.ajpath.2015.04.021. View

3.
Cieply B, Zeng G, Proverbs-Singh T, Geller D, Monga S . Unique phenotype of hepatocellular cancers with exon-3 mutations in beta-catenin gene. Hepatology. 2008; 49(3):821-31. PMC: 2657345. DOI: 10.1002/hep.22695. View

4.
Parviz F, Matullo C, Garrison W, Savatski L, Adamson J, Ning G . Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat Genet. 2003; 34(3):292-6. DOI: 10.1038/ng1175. View

5.
Amit S, Hatzubai A, Birman Y, Andersen J, Ben-Shushan E, Mann M . Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev. 2002; 16(9):1066-76. PMC: 186245. DOI: 10.1101/gad.230302. View