Glutamine synthetase loss in β-catenin–mutant hepatocellular carcinoma promotes tumor burden through macrophage metabolic reprogramming
We demonstrate the unique metabolic dependency of β-catenin-mutated HCCs on GS in tumor cells, which is diverted to macrophages upon GS elimination in tumor cells. This adaptation alters macrophage metabolism and function, leading to compromised immunosurveillance and greater tumor burden. Our study reveals a metabolic dynamic between HCC cells and macrophages with an impact on tumor biology.
Authors
- Junyan Tao (ORCID: https://orcid.org/0000-0002-5249-970X)
- Daniel M. Green (ORCID: https://orcid.org/0000-0002-5156-5410)
- Panari Patel
- Sucha Singh (ORCID: https://orcid.org/0000-0002-9131-1423)
- Aatur Dilip Singhi (ORCID: https://orcid.org/0000-0003-3930-7096)
- Brandon M. Lehrich (ORCID: https://orcid.org/0000-0003-1003-5605)
- Silvia Liu (ORCID: https://orcid.org/0000-0002-1840-9520)
- Yekaterina Krutsenko (ORCID: https://orcid.org/0000-0002-7011-6469)
- Satdarshan P. Monga (ORCID: https://orcid.org/0000-0002-8437-3378)
- Evan R. Delgado (ORCID: https://orcid.org/0000-0003-2706-0946)
- Aaron Bell (ORCID: https://orcid.org/0000-0001-6648-0834)
- Vik Meadows (ORCID: https://orcid.org/0000-0002-8983-4305)
- Tyler M. Yasaka (ORCID: https://orcid.org/0000-0002-8482-0369)
- Jia‐Lin Liu (ORCID: https://orcid.org/0000-0003-4544-0627)
- Xin Chen (ORCID: https://orcid.org/0000-0002-9588-0164)
- Minakshi Poddar
- Raghad Alzubali
Institutions
- University of Hawaiʻi at Mānoa (US)
- University of Hawaii System (US)
- University of Pittsburgh (US)
- Cancer Center of Hawaii (US)
- UPMC Hillman Cancer Center (US)
- University of Pittsburgh Medical Center (US)
- University of Hawaii Cancer Center
Publication Details
- Journal
- Hepatology
- Published
- 2025-10-23
- DOI
- https://doi.org/10.1097/hep.0000000000001591
- Citations
- 1
- Primary Topic
- Cancer, Hypoxia, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.94