FOXA1 suppresses breast cancer progression by downregulating CYP4Z1-mediated lipid metabolic reprogramming

Breast cancer progression is closely associated with metabolic imbalance, particularly lipid metabolic reprogramming, which supports tumour growth. This study investigated the expression of CYP4Z1, a member of the cytochrome P450 family, in breast cancer cells and its role in tumour progression. CYP4Z1 was markedly overexpressed in breast cancer tissues and strongly associated with poor patient prognosis. Functional experiments revealed that CYP4Z1 silencing inhibited proliferation, migration and epithelial–mesenchymal transition while promoting apoptosis and senescence in breast cancer cells; in contrast, CYP4Z1 overexpression enhanced malignant behaviour. Nontargeted lipidomics revealed that CYP4Z1 downregulation disrupted lipid homeostasis, particularly by inducing triglyceride accumulation, suggesting its importance in maintaining tumour lipid metabolism. Mechanistically, bioinformatics analysis and dual-luciferase assays confirmed that FOXA1 represses CYP4Z1 promoter activity. The loss of FOXA1 activated CYP4Z1, triggered lipid metabolic reprogramming and promoted malignant phenotypes. Rescue experiments further demonstrated that CYP4Z1 silencing reversed the proliferation, migration and abnormal lipid accumulation induced by FOXA1 deficiency. Overall, these findings suggest that CYP4Z1 may contribute to breast cancer progression in association with lipid metabolic remodelling and support the involvement of the FOXA1–CYP4Z1 axis in this process. This axis may represent a candidate mechanism warranting further investigation in translational studies.