{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317428/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317428"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"PGK1 acts as a non-catalytic gatekeeper of ferroptosis by stabilizing SLC7A11","description":"Ferroptosis is restrained by layered antioxidant defenses, yet whether glycolytic enzymes directly constitute ferroptosis-defense machinery remains unclear. Here we identify phosphoglycerate kinase 1 (PGK1) as a non-canonical suppressor of ferroptosis that functions independently of its glycolytic kinase activity. Across pan-cancer bulk and single-cell transcriptomes, glycolysis inversely associates with ferroptosis programs, with PGK1 emerging as a prognostic hub. PGK1 loss in multiple tumor models elicits hallmark ferroptotic features, elevates lipid peroxidation and labile iron, and suppresses xenograft growth, all of which are reversed by liproxstatin-1. Mechanistically, PGK1 physically binds the C-terminal tail of SLC7A11 (aa 471-501) and shields it from ubiquitin-proteasome degradation, thereby sustaining cystine-driven glutathione synthesis and redox homeostasis. This scaffolding role is preserved in a kinase-dead PGK1 mutant, establishing a strict separation between metabolic and ferroptosis-regulatory functions. Restoring SLC7A11 rescues PGK1-deficient tumor growth, whereas a rationally designed competing peptide SLC7A11471-501 (FP-01) disrupts the PGK1-SLC7A11 interface, depletes SLC7A11/GSH, triggers ferroptosis, and suppresses tumor progression in vivo. Collectively, the PGK1-SLC7A11 interaction represents a druggable ferroptosis vulnerability that enables selective ferroptosis induction while sparing essential glycolysis.","dates":{"publication":"2026/07/12"},"accession":"GSE317428","cross_references":{"GSM":["GSM9472081","GSM9472082","GSM9472080","GSM9472078","GSM9472079","GSM9472077"],"GPL":["24676"],"GSE":["317428"],"taxon":["Homo sapiens"]}}