ArticleThe Journal of clinical investigation2021
Targeting the mitochondrial trifunctional protein restrains tumor growth in oxidative lung carcinomas.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 41 citations in OpenAlex.
- Intermediate accumulated upon interruption of fatty acid oxidation flux promotes tumoral ferroptosis and improves immunotherapy.Nature communications · 2026Article
- Melatonin targets mitochondrial trifunctional enzyme HADHA to improve lipid metabolism in metabolic dysfunction-associated steatotic liver disease.Molecular biomedicine · 2026Article
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Long-term risk of malignancies in persons with ischemic heart disease treated with trimetazidine dihydrochloride.Communications medicine · 2025Article
- Management succinate release through SDHA by G protein-coupled receptor 91 signal, TRAP1, and SIRT3 regulation in lung cancer cells by NAR nanoparticles.Journal, genetic engineering & biotechnology · 2025Article
- Carnitine O-Acetyltransferase as a Central Player in Lipid and Branched-Chain Amino Acid Metabolism, Epigenetics, Cell Plasticity, and Organelle Function.Biomolecules · 2025Review
- MiR-26a Inhibits Porcine Adipogenesis by Regulating ACADM and ACSL1 Genes and Cell Cycle Progression.Animals : an open access journal from MDPI · 2024Article
- HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- HADHA promotes esophageal cancer progression by activating mTOR signaling and the SP1/MDM2 axis.Acta biochimica et biophysica Sinica · 2024Article
- Pioglitazone, a peroxisome proliferator‑activated receptor γ agonist, induces cell death and inhibits the proliferation of hypoxic HepG2 cells by promoting excessive production of reactive oxygen species.Oncology letters · 2024Article
- Article
- PaSTe. Blockade of the Lipid Phenotype of Prostate Cancer as Metabolic Therapy: A Theoretical Proposal.Current medicinal chemistry · 2024Review
- The Mitochondrial ATP Synthase/IF1 Axis in Cancer Progression: Targets for Therapeutic Intervention.Cancers · 2023Review
- Molecular targets of spermidine: implications for cancer suppression.Cell stress · 2023Article
- Combining the antianginal drug perhexiline with chemotherapy induces complete pancreatic cancer regressioniScience · 2023Article
- Impairment of electron transport chain and induction of apoptosis by chrysin nanoparticles targeting succinate-ubiquinone oxidoreductase in pancreatic and lung cancer cells.Genes & nutrition · 2023Article
- Targeting lipid metabolism in metastatic prostate cancer.Therapeutic advances in medical oncology · 2023Review
- Genetics of enzymatic dysfunctions in metabolic disorders and cancer.Frontiers in oncology · 2023Review
- The "sweet" path to cancer: focus on cellular glucose metabolism.Frontiers in oncology · 2023Review
- UCP2 as a Cancer Target through Energy Metabolism and Oxidative Stress Control.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic reprogramming is a common hallmark of cancer, but a large variability in tumor bioenergetics exists between patients. Using high-resolution respirometry on fresh biopsies of human lung adenocarcinoma, we identified 2 subgroups reflected in the histologically normal, paired, cancer-adjacent tissue: high (OX+) mitochondrial respiration and low (OX-) mitochondrial respiration. The OX+ tumors poorly incorporated [18F]fluorodeoxy-glucose and showed increased expression of the mitochondrial trifunctional fatty acid oxidation enzyme (MTP; HADHA) compared with the paired adjacent tissue. Genetic inhibition of MTP altered OX+ tumor growth in vivo. Trimetazidine, an approved drug inhibitor of MTP used in cardiology, also reduced tumor growth and induced disruption of the physical interaction between the MTP and respiratory chain complex I, leading to a cellular redox and energy crisis. MTP expression in tumors was assessed using histology scoring methods and varied in negative correlation with [18F]fluorodeoxy-glucose incorporation. These findings provide proof-of-concept data for preclinical, precision, bioenergetic medicine in oxidative lung carcinomas.
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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.