Authors
Xingyu Zhou, Chuanfa Liu, Wenchao Wei, Xueliang Wang, Yasi Pan, Ying Jiao, Shiyu Li, Yating Zhang, Harry Cheuk-Hay Lau, Ruyi Zhang, Dingwu Li, Alvin Ho-Kwan Cheung, Minghua Zheng, Wen Pan, Chi Chun Wong, Vincent Wai-Sun Wong, Jun Yu, Xiang Zhang
Published in
Cell metabolism. Oct 02, 2026. Epub Oct 02, 2026.
Abstract
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. 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.
PMID:
42826714
Bibliographic data and abstract were imported from PubMed on 03 Oct 2026.
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