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GPR35-mediated metabolic reprogramming promotes tumorigenesis in digestive cancers
Fang Wang1, Xin-Xin Ding1, Tao-Hong Su1
1Cancer Research Center, The Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, China.
Frontiers in Immunology
|December 29, 2025
Summary
G protein-coupled receptor 35 (GPR35) regulates tumor metabolism and immunity in digestive cancers. Targeting GPR35 offers a promising therapeutic strategy for these aggressive malignancies.
Area of Science:
- Oncology
- Molecular Biology
- Metabolism
Background:
- G protein-coupled receptor 35 (GPR35) is implicated in tumor metabolism and immune modulation.
- Aberrant GPR35 expression correlates with poor prognosis in digestive system cancers.
Purpose of the Study:
- To review GPR35's role in metabolic reprogramming within the tumor microenvironment.
- To explore GPR35's function as an interface between host cells and gut microbiota in cancer progression.
- To discuss the therapeutic potential and challenges of targeting GPR35.
Main Methods:
- Comprehensive literature review of GPR35's functions in cancer metabolism and immunity.
- Analysis of GPR35's involvement in glucose, lipid, amino acid, and microbial metabolite metabolism.
- Examination of GPR35's influence on tumor microenvironment factors like angiogenesis and inflammation.
Main Results:
- GPR35 significantly impacts metabolic reprogramming, influencing key nutrients and microbial metabolites.
- GPR35 modulates the tumor microenvironment by affecting angiogenesis, immune cell infiltration, and inflammation.
- GPR35 acts as a crucial link between host cells and gut microbiota, promoting cancer via microbial metabolites.
Conclusions:
- Targeting GPR35-mediated metabolic reprogramming presents a novel therapeutic strategy for digestive cancers.
- Challenges in GPR35 drug development include species-specific effects and ligand selectivity.
- Humanized GPR35 models are advancing translational research for optimizing GPR35-specific therapeutics.
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