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Infectious Agents Induce Wnt/β-Catenin Pathway Deregulation in Primary Liver Cancers
Teresa Catalano1, Federico Selvaggi2, Diana Liberata Esposito3,4
1Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy.
Microorganisms
|July 29, 2023
Summary
Infectious agents disrupt liver cells by altering Wnt/β-catenin signaling, increasing primary liver cancer (PLC) risk. Targeting this pathway offers potential new PLC treatments.
Area of Science:
- Hepatology
- Oncology
- Microbiology
Background:
- Primary liver cancers (PLCs), mainly hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), arise from interactions between infectious agents and liver tissue.
- Infectious agents can destabilize liver cell functions by modulating the Wnt/β-catenin pathway, a critical signaling cascade in cell development and cancer.
- Several hepatotropic viruses (B, C, D), oncogenic viruses (EBV, HPV), bacteria, protozoa, fungi, and liver flukes are implicated in PLC development through Wnt signaling dysregulation.
Purpose of the Study:
- To review new insights into infectious agents that deregulate Wnt signaling.
- To explore the role of Wnt/β-catenin pathway modulation by various microbes in primary liver cancer development.
- To highlight the potential of targeting the Wnt signaling pathway for novel therapeutic strategies against PLCs.
Main Methods:
- Literature review focusing on infectious agents and their impact on Wnt/β-catenin signaling in liver cancer.
- Analysis of mechanisms by which microbial agents dysregulate Wnt signaling components.
- Synthesis of current understanding of the link between infection, Wnt signaling, and PLC pathogenesis.
Main Results:
- Hepatotropic viruses (Hepatitis B, C, D) directly impact Wnt/β-catenin signaling.
- Other infectious agents including Epstein-Barr virus, human papilloma virus, Mycoplasma hyorhinis, Salmonella Typhi, Toxoplasma gondii, Aspergillus flavus, Clonorchis sinensis, and Opisthorchis viverrini also activate aberrant Wnt signaling.
- Aberrant Wnt signaling activation by these agents contributes to malignant transformation in hepatocytes and biliary tract cells.
Conclusions:
- The Wnt/β-catenin pathway is a key mediator in cancer development following various infections.
- Infectious agents play a significant role in the etiology of primary liver cancers through Wnt signaling disruption.
- Inhibitors of the Wnt signaling pathway represent promising therapeutic targets for treating primary liver cancers.
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