CPT1A Over-Expression Increases Reactive Oxygen Species in the Mitochondria and Promotes Antioxidant Defenses in Prostate Cancer.

Cancers
Molishree JoshiIsabel R Schlaepfer

Abstract

Cancers reprogram their metabolism to adapt to environmental changes. In this study, we examined the consequences of altered expression of the mitochondrial enzyme carnitine palmitoyl transferase I (CPT1A) in prostate cancer (PCa) cell models. Using transcriptomic and metabolomic analyses, we compared LNCaP-C4-2 cell lines with depleted (knockdown (KD)) or increased (overexpression (OE)) CPT1A expression. Mitochondrial reactive oxygen species (ROS) were also measured. Transcriptomic analysis identified ER stress, serine biosynthesis and lipid catabolism as significantly upregulated pathways in the OE versus KD cells. On the other hand, androgen response was significantly downregulated in OE cells. These changes associated with increased acyl-carnitines, serine synthesis and glutathione precursors in OE cells. Unexpectedly, OE cells showed increased mitochondrial ROS but when challenged with fatty acids and no androgens, the Superoxide dismutase 2 (SOD2) enzyme increased in the OE cells, suggesting better antioxidant defenses with excess CPT1A expression. Public databases also showed decreased androgen response correlation with increased serine-related metabolism in advanced PCa. Lastly, worse progression free survival was obser...Continue Reading

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Citations

Jan 13, 2021·Cancers·Claudia Manini, José I López
Aug 14, 2021·Frontiers in Oncology·Natalia ScagliaGiorgia Zadra

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Datasets Mentioned

BETA
GSE32967
GSE161243

Methods Mentioned

BETA
acetylation
histone acetylation
proteins folding
RNAseq
xenografts
protein assay
Assay

Software Mentioned

survminer
Xenon
GSVA R package
GraphPad
ComplexHeatmap R package
MetaboAnalyst
limma R package
GraphPad Prism
fGSEA R package
GSEA

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