ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Genome-Wide CRISPR/Cas9 Library Screening Revealed Dietary Restriction of Glutamine in Combination with Inhibition of Pyruvate Metabolism as Effective Liver Cancer Treatment.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Cuproptosis: A Potential Target for the Treatment of Systemic Lupus Erythematosus.Journal of inflammation research · 2026Review
- Riboflavin-PLGA nanoparticles enhance the effectiveness of the pyruvate carboxylase inhibitor ZY-444 in targeting lipogenesis in colon and breast cancer.Scientific reports · 2025Article
- Unveiling the metal-driven death: ferroptosis and cuproptosis in leukemia.European journal of medical research · 2025Review
- Cuproptosis: the mechanisms of copper-induced cell death and its implication in colorectal cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- In silico development and validation of a novel six-gene-derived signature in hepatocellular carcinoma.Translational cancer research · 2025Article
- PLOD1 promotes the malignancy of hepatocellular carcinoma by facilitating the NF-κB/IL-6/STAT3-dependent TCA cycle.JHEP reports : innovation in hepatology · 2025Article
- Construction of a treatment response prediction model for multiple myeloma based on multi-omics and machine learning.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Activation of PI3K-AKT pathway prevents steroid-induced osteonecrosis of the femoral head via inhibiting Cuproptosis.Scientific reports · 2025Article
- PathSynergy: a deep learning model for predicting drug synergy in liver cancer.Briefings in bioinformatics · 2025Article
- CEP55: Implications for Immunotherapy and Survival in Hepatocellular Carcinoma.Combinatorial chemistry & high throughput screening · 2025Article
- CRISPR-Cas and CRISPR-based screening system for precise gene editing and targeted cancer therapy.Journal of translational medicine · 2024Review
- tRF-1:30-Gly-CCC-3 inhibits thyroid cancer via binding to PC and modulating metabolic reprogramming.Life science alliance · 2024Article
- Genome-wide loss-of-function genetic screen identifies INSIG2 as the vulnerability of hepatitis B virus-integrated hepatoma cells.Cancer science · 2024Article
- Analysis of the potential biological value of pyruvate dehydrogenase E1 subunit β in human cancer.World journal of gastrointestinal oncology · 2024Article
- Novel cuproptosis-related prognostic gene profiles in preeclampsia.BMC pregnancy and childbirth · 2024Article
- A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma.Oncology research · 2024Review
- Impact of Cuproptosis-related markers on clinical status, tumor immune microenvironment and immunotherapy in colorectal cancer: A multi-omic analysis.Computational and structural biotechnology journal · 2023Article
- A cuproptosis random forest cox score model-based evaluation of prognosis, mutation characterization, immune infiltration, and drug sensitivity in hepatocellular carcinoma.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the second most lethal cancer worldwide. Glutamine is an essential, extracellular nutrient which supports HCC growth. Dietary glutamine deficiency may be a potential therapeutic approach for HCC. HCC cells overcome metabolic challenges by rewiring their metabolic pathways for rapid adaptations. The efficiency of dietary glutamine deficiency as HCC treatment is examined and the adaptation machinery under glutamine depletion in HCC cells is unraveled. Using genome-wide CRISPR/Cas9 knockout library screening, this study identifies that pyruvate dehydrogenase α (PDHA), pyruvate dehydrogenase β (PDHB), and pyruvate carboxylase (PC) in pyruvate metabolism are crucial to the adaptation of glutamine depletion in HCC cells. Knockout of either PDHA, PDHB or PC induced metabolic reprogramming of the tricarboxylic acid (TCA) cycle, disrupts mitochondrial function, leading to the suppression of HCC cell proliferation under glutamine depletion. Surprisingly, dietary glutamine restriction improves therapeutic responses of HCC to PDH or PC inhibitor in mouse HCC models. Stable isotope carbon tracing confirms that PDH or PC inhibitors further disrupt the metabolic rewiring of the TCA cycle induced by dietary glutamine depletion in HCC. In summary, the results demonstrate that pyruvate metabolism acts as novel targetable metabolic vulnerabilities for HCC treatment in combination with a glutamine-deficient diet.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.