3 Key Takeaways
Plain English Summary- 01Core Finding
Here, we investigated the role of fungi in metabolic dysfunction-associated steatotic liver disease-associated hepatocellular carcinoma (MASLD-HCC).
- 02Study Evidence
Tested in a in vivo animal model (preclinical discovery) at the preclinical stage.
- 03Practical Meaning
Early laboratory or animal model findings — human trials are still needed to confirm safety and benefit.
What This Means for You
Mechanistically, KYNA directly bound to IQ motif containing GTPase activating protein 1 (IQGAP1) in tumor cells and activated the oncogenic mitogen-activated protein kinase (MAPK) signaling pathway, thereby facilitating MASLD-HCC development. In summary, R. arrhizus is a pathogenic fungus that promotes MASLD-HCC by producing KYNA.
Blocking this host-fungi interaction is a potential therapeutic strategy to suppress MASLD-HCC.
The Discovery
Fungi are crucial components of the human gut microbiota. Here, we investigated the role of fungi in metabolic dysfunction-associated steatotic liver disease-associated hepatocellular carcinoma (MASLD-HCC). Rhizopus arrhizus was the top enriched fungus across the progression from MASLD to MASLD-HCC, accelerating tumorigenesis in multiple mouse models. R. arrhizus-conditioned medium increased cell proliferation while reducing cell cycle arrest and apoptosis in human MASLD-HCC cells. Kynurenic acid (KYNA) was identified as the crucial metabolite generated from R. arrhizus, and its upregulation was confirmed in portal vein, liver tissues, and stools of R. arrhizus-treated mice. KYNA promoted the proliferation of MASLD-HCC cells and accelerated tumorigenesis in mice.
How It Works, Simply
This endocrinology research focuses on signalling pathway. Researchers evaluated it using an in vivo animal model (Preclinical discovery) at the preclinical stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Here, we investigated the role of fungi in metabolic dysfunction-associated steatotic liver disease-associated hepatocellular carcinoma (MASLD-HCC).
- 02Study Evidence
Tested in a in vivo animal model (preclinical discovery) at the preclinical stage.
- 03Practical Meaning
Early laboratory or animal model findings — human trials are still needed to confirm safety and benefit.
Biological Mechanism & Study Design
Study Design & Cohort
Animal models
In vivo animal model (Preclinical discovery) · Preclinical
Biological Pathway & Modality
Signalling pathway
Intervention: Fungus Rhizopus arrhizus promotes MASLD-associated hepatocellular carcinoma through
Experimental Findings & Endpoints
Fungi are crucial components of the human gut microbiota.
Here, we investigated the role of fungi in metabolic dysfunction-associated steatotic liver disease-associated hepatocellular carcinoma (MASLD-HCC). Rhizopus arrhizus was the top enriched fungus across the progression from MASLD to MASLD-HCC, accelerating tumorigenesis in multiple mouse models.
R. arrhizus-conditioned medium increased cell proliferation while reducing cell cycle arrest and apoptosis in human MASLD-HCC cells. Kynurenic acid (KYNA) was identified as the crucial metabolite generated from R. arrhizus, and its upregulation was confirmed in portal vein, liver tissues, and stools of R. arrhizus-treated mice.
KYNA promoted the proliferation of MASLD-HCC cells and accelerated tumorigenesis in mice.
Clinical Translation & Practice Context
Mechanistically, KYNA directly bound to IQ motif containing GTPase activating protein 1 (IQGAP1) in tumor cells and activated the oncogenic mitogen-activated protein kinase (MAPK) signaling pathway, thereby facilitating MASLD-HCC development.
In summary, R. arrhizus is a pathogenic fungus that promotes MASLD-HCC by producing KYNA.
Blocking this host-fungi interaction is a potential therapeutic strategy to suppress MASLD-HCC.
The Bottom Line · Clinical Pearl
“Blocking this host-fungi interaction is a potential therapeutic strategy to suppress MASLD-HCC.”
Published in Cell Metabolism · Current Stage: Preclinical