The role of lactate metabolism in retinoblastoma tumorigenesis and ferroptosis resistance
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View abstract on PubMed
Summary
This summary is machine-generated.Lactate metabolism fuels retinoblastoma growth and ferroptosis resistance by upregulating monocarboxylate transporter 1 (MCT1). Inhibiting MCT1 suppresses tumor progression and invasion, offering a potential therapeutic target for this childhood eye cancer.
Area Of Science
- Oncology
- Metabolic Research
- Ophthalmology
Background
- The Warburg effect, characterized by aerobic glycolysis and lactate accumulation, is common in cancers but its role in retinoblastoma is poorly understood.
- Retinoblastoma is the most common primary intraocular malignancy in children.
Purpose Of The Study
- To investigate the role of lactate metabolism in retinoblastoma.
- To analyze gene expression profiles related to lactate metabolism in retinoblastoma.
- To determine the impact of lactate metabolism on retinoblastoma tumorigenesis and ferroptosis resistance.
Main Methods
- Single-cell RNA sequencing of normal retina and retinoblastoma tissues.
- In vitro and in vivo studies on retinoblastoma cell lines and a mouse xenograft model.
- Analysis of lactate's effect on cell viability, ferroptosis, and monocarboxylate transporter 1 (MCT1) expression.
- MCT1 knockdown and inhibition experiments.
Main Results
- Retinoblastoma cells exhibit enhanced glycolysis and distinct lactate metabolism gene expression profiles.
- Moderate lactate levels increased retinoblastoma cell viability and ferroptosis resistance.
- Lactate upregulated MCT1, facilitating lactate transport and enhancing cell survival.
- MCT1 inhibition or knockdown reduced retinoblastoma viability and ferroptosis resistance.
- In vivo, MCT1 inhibition suppressed retinoblastoma growth and invasion, an effect reversed by a ferroptosis inhibitor.
Conclusions
- Lactate metabolism plays a critical role in retinoblastoma tumorigenesis and ferroptosis resistance.
- Upregulation of MCT1 is a key mechanism by which lactate promotes retinoblastoma progression.
- Targeting lactate transport via MCT1 inhibition presents a potential therapeutic strategy for retinoblastoma.
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