ArticleMolecular biology reports2023
c-Myc protects hepatocellular carcinoma cell from ferroptosis induced by glutamine deprivation via upregulating GOT1 and Nrf2.
Article in Molecular biology reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 22 citations in OpenAlex.
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Immunometabolic Reprogramming in Hepatocellular Carcinoma Mechanisms, Biomarkers, and Therapeutic Implications.Oncology research · 2026Review
- Metabolic control of ferroptosis in cancer: lipid dependencies as therapeutic vulnerabilities.Frontiers in oncology · 2026Review
- Phenotypic Response Surfaces-Guided Optimization (PRS-OPT) of Propolis-Metformin-Regorafenib Combination Therapy for MASLD-Associated Hepatocellular Carcinoma.Oncology research · 2026Article
- Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics.International journal of medical sciences · 2026Review
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Article
- Regulation of ferroptosis by transcription factor E2F1.Biochimie · 2025Article
- Exploring the multifaceted roles of glutamate oxaloacetate transaminase 1 as a biomarker and therapeutic target in colorectal cancer and pan-cancer analyses.Discover oncology · 2025Article
- The spatiotemporal heterogeneity of reactive oxygen species in the malignant transformation of viral hepatitis to hepatocellular carcinoma: a new insight.Cellular & molecular biology letters · 2025Review
- c-Myc-dependent LAMP3 regulates the proliferation, metastasis and metabolic reprogramming of tongue squamous cell carcinoma.Scientific reports · 2025Article
- JS-K induces ferroptosis in renal carcinoma cells by regulating the c-Myc-GSTP1 Axis.Scientific reports · 2025Article
- Ferroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy.Cell proliferation · 2025Review
- Identification of novel ferroptosis-related biomarkers associated with the oxidative stress pathways in ischemic cardiomyopathy.International journal of cardiology. Heart & vasculature · 2025Article
- Identification of STAT3 and MYC as critical ferroptosis-related biomarkers in septic cardiomyopathy: a bioinformatics and experimental study.Journal of molecular medicine (Berlin, Germany) · 2025Article
- A glutamine metabolish-associated prognostic model to predict prognosis and therapeutic responses of hepatocellular carcinoma.Biology direct · 2024Article
- Ferroptosis: a new promising target for hepatocellular carcinoma therapy.Molecular and cellular biochemistry · 2024Review
- AGC1-mediated Metabolic Reprogramming and Autophagy Sustain Survival of Hepatocellular Carcinoma Cells under Glutamine Deprivation.Cell biochemistry and biophysics · 2024Article
- Ferroptosis and its relationship with cancer.Frontiers in cell and developmental biology · 2024Review
- Dual role of Nrf2 signaling in hepatocellular carcinoma: promoting development, immune evasion, and therapeutic challenges.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGlutamine metabolism is critical for development of hepatocellular carcinoma (HCC), which makes it a novel promising treatment target. However, clinical evidence suggested glutamine withdrawal therapy does not achieved the desired tumor suppression. Therefore, it is valuable to investigate the survival mechanisms of tumors with glutamine deprivation.
methodsThe HCC cells were cultured in glutamine-free medium or supplemented with glutamine metabolites or ferroptosis inhibitors. The parameters related to ferroptosis and the activity of GSH synthesis-related enzymes of the HCC cells were detected by corresponding kits. The expressions of glutamate oxaloacetate transaminase 1 (GOT1), c-Myc and Nrf2 were detected by western blot and qRT-PCR. The chromatin immunoprecipitation and luciferase reporter assays were performed to investigate the correlation between c-Myc and GOT1. The siRNAs of c-Myc and GOT1 were used to explore their roles in GSH (GSH) synthesis and ferroptosis in vitro and in vivo.
resultsGlutamine deprivation-induced ferroptosis did not completely inhibit HCC cells proliferation. Glutamine deprivation activated the expression of c-Myc, which promoted the transcription of GOT1 and Nrf2, consequently maintaining the GSH synthesis and inhibiting ferroptosis. In addition, combined inhibition of GOT1 with glutamine deprivation could result in better inhibition of HCC in vitro and in vivo.
conclusionsIn our work, the results indicate that GOT1 induced by c-Myc may play an important role in combating ferroptosis due to glutamine deprivation, making it a significant target in glutamine withdrawal therapy. This study provides a theoretical foundation for the clinical targeted therapy for HCC.
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