Targeting carbonic anhydrase IX/XII prevents the anti-ferroptotic effect of stromal lactic acid in prostate carcinoma.

ABSTRACT: Ferroptosis is a form of regulated cell death dependent on iron-driven phospholipid peroxidation and is controlled by both cell autonomous and non-cell autonomous mechanisms. In prostate cancer (PCa), tumor cells engage in a metabolic crosstalk with cancer-associated fibroblasts (CAFs), resulting in increased utilization of CAF-secreted lactic acid, that ultimately supports cancer aggressiveness. In this context, the effect of the prostate tumor microenvironment in modulating ferroptosis sensitivity has not yet been extensively investigated. Here, we demonstrate that CAF-secreted lactic acid protects PCa cells from ferroptosis induction and supports the upregulation of the antioxidant enzyme glutathione peroxidase 4 (GPX4). Interestingly, targeting carbonic anhydrase IX/XII (CA IX/XII), th

SUBMITTER: Pardella E 

PROVIDER: S-EPMC12420354 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature