Targeting the mitochondrial trifunctional protein restrains tumor growth in oxidative lung carcinomas
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View abstract on PubMed
Summary
This summary is machine-generated.Lung adenocarcinoma tumors show distinct bioenergetic profiles. Inhibiting the mitochondrial trifunctional fatty acid oxidation enzyme (MTP) reduced tumor growth, offering a precision medicine approach.
Area Of Science
- Oncology
- Biochemistry
- Metabolic Medicine
Background
- Metabolic reprogramming is a hallmark of cancer, yet significant patient-to-patient variability exists in tumor bioenergetics.
- Understanding these bioenergetic differences is crucial for developing targeted cancer therapies.
Purpose Of The Study
- To investigate the bioenergetic heterogeneity in human lung adenocarcinoma.
- To identify specific metabolic pathways and enzymes associated with different tumor respiration states.
- To explore the therapeutic potential of targeting fatty acid oxidation in lung cancer.
Main Methods
- High-resolution respirometry on fresh human lung adenocarcinoma biopsies.
- Analysis of [18F]fluorodeoxy-glucose ([18F]FDG) uptake and mitochondrial trifunctional enzyme (MTP; HADHA) expression.
- In vivo studies involving genetic inhibition of MTP and treatment with trimetazidine.
- Assessment of MTP expression via histology scoring.
Main Results
- Two subgroups of lung adenocarcinoma were identified based on mitochondrial respiration: high (OX+) and low (OX-).
- OX+ tumors exhibited poor [18F]FDG uptake and increased MTP expression.
- Genetic MTP inhibition and trimetazidine treatment reduced OX+ tumor growth.
- Trimetazidine disrupted MTP interaction with respiratory chain complex I, causing cellular redox and energy crisis.
Conclusions
- Lung adenocarcinoma displays distinct bioenergetic phenotypes linked to MTP activity.
- MTP is a potential therapeutic target for precision bioenergetic medicine in lung cancer.
- Targeting MTP offers a novel strategy for treating oxidative lung carcinomas.
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