ArticleCell death and differentiation2018
The mitochondrial citrate carrier, SLC25A1, drives stemness and therapy resistance in non-small cell lung cancer.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- The role of lipid metabolic reprogramming in tumor microenvironment.Theranostics · 2023Pooled it
- Mitochondrial metabolite transporters at the crossroads of metabolic reprogramming, epigenetic regulation and therapeutic vulnerabilities in colorectal cancer.Molecular biology reports · 2026Review
- Article
- Decoding the metabolic cipher of dormant cancer cells: molecular mechanisms and therapeutic potentials.Cell communication and signaling : CCS · 2026Review
- SLC25A1 upregulation promotes HNSCC cisplatin resistance via H3K27ac-mediated cellular senescence.NPJ precision oncology · 2026Article
- SLC25A1 reprograms mitochondrial and fatty acid metabolism to promote the progression of acute myeloid leukemia.Haematologica · 2026Article
- Harnessing Machine Learning and Multiomics to Construct a Tumor-Specific T Cell Signature for Prognostic Assessment and Precision Medicine in Lung Adenocarcinoma.Annals of surgical oncology · 2026Article
- Targeting Lung Cancer Metabolism: Therapeutic Opportunities and Challenges.Advances in experimental medicine and biology · 2026Review
- SLC25A1-Mediated Cholesterol Accumulation Promotes Endometriosis Progression by Enhancing Endometrial Stromal Cell Proliferation, Invasion, and M2 Macrophage Polarization.International journal of biological sciences · 2026Article
- Metabolic reprogramming signature predicts immunotherapy efficacy in lung adenocarcinoma: TargetingChinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Inhibition of scheggia/SLC25A1 citrate transporter alleviates XPD deficits.Scientific reports · 2025Article
- Mechanistically informed machine learning links non-canonical TCA cycle activity to Warburg metabolism and hallmarks of malignancy.PLoS computational biology · 2025Article
- Exploring the significance of fatty acid metabolism reprogramming in the pathogenesis of cancer and anticancer therapy.Annals of medicine · 2025Review
- Itaconate transport across the plasma membrane and Salmonella-containing vacuole via MCT1/4 modulates macrophage antibacterial activity.Nature communications · 2025Article
- Intracellular Salmonella hijacks the mitochondrial citrate carrier to evade host oxidative defenses.Nature communications · 2025Article
- The integral membrane protein smim4 modulates redox balance via malate compartmentalization in pancreatic cancer.Nature communications · 2025Article
- Targeting mitochondrial transporters and metabolic reprogramming for disease treatment.Journal of translational medicine · 2025Review
- Article
- Targeting iron regulatory protein 2 (IRP2) to disrupt iron metabolism enhances radiosensitivity through mitochondrial dysfunction in breast cancer cells.Cell death discovery · 2025Article
- Oxidative Stress Defense Module in Lung Cancers: Molecular Pathways and Therapeutic Approaches.Antioxidants (Basel, Switzerland) · 2025Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
Therapy resistance represents a clinical challenge for advanced non-small cell lung cancer (NSCLC), which still remains an incurable disease. There is growing evidence that cancer-initiating or cancer stem cells (CSCs) provide a reservoir of slow-growing dormant populations of cells with tumor-initiating and unlimited self-renewal ability that are left behind by conventional therapies reigniting post-therapy relapse and metastatic dissemination. The metabolic pathways required for the expansion of CSCs are incompletely defined, but their understanding will likely open new therapeutic opportunities. We show here that lung CSCs rely upon oxidative phosphorylation for energy production and survival through the activity of the mitochondrial citrate transporter, SLC25A1. We demonstrate that SLC25A1 plays a key role in maintaining the mitochondrial pool of citrate and redox balance in CSCs, whereas its inhibition leads to reactive oxygen species build-up thereby inhibiting the self-renewal capability of CSCs. Moreover, in different patient-derived tumors, resistance to cisplatin or to epidermal growth factor receptor (EGFR) inhibitor treatment is acquired through SLC25A1-mediated implementation of mitochondrial activity and induction of a stemness phenotype. Hence, a newly identified specific SLC25A1 inhibitor is synthetic lethal with cisplatin or with EGFR inhibitor co-treatment and restores antitumor responses to these agents in vitro and in animal models. These data have potential clinical implications in that they unravel a metabolic vulnerability of drug-resistant lung CSCs, identify a novel SLC25A1 inhibitor and, lastly, provide the first line of evidence that drugs, which block SLC25A1 activity, when employed in combination with selected conventional antitumor agents, lead to a therapeutic benefit.
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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.