Cyclin-dependent kinase 12 deficiency reprogrammes cellular metabolism to alleviate ferroptosis potential and promote the progression of castration-resistant prostate cancer.
Haozhe ZhangYi ZhouYating FengWenli HouYafei ChenZengzhen XingYifan ZhangQiang WeiYu YinJu GuoHailiang HuPublished in: Clinical and translational medicine (2024)
CDK12 deficiency promotes castration-resistant prostate cancer (CRPC) progression by reprogramming cellular metabolism. CDK12 deficiency in CRPC leads to a more active mitochondrial electron transport chain (ETC), ensuring efficient cell energy supply. CDK12 phosphorylates RNA Pol II to ensure the transcription of ACSL4 to regulate ferroptosis. Mitochondrial ETC inhibitors exhibit better selectivity for CDK12-deficient CRPC cells, offering a promising new therapeutic approach for this subtype of CRPC patients.
Keyphrases
- cell cycle
- cell death
- cell cycle arrest
- end stage renal disease
- oxidative stress
- ejection fraction
- induced apoptosis
- newly diagnosed
- cell proliferation
- chronic kidney disease
- replacement therapy
- prognostic factors
- single cell
- peritoneal dialysis
- transcription factor
- cell therapy
- mesenchymal stem cells
- tyrosine kinase
- endoplasmic reticulum stress
- smoking cessation