{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["16"],"submitter":["Li J"],"pubmed_abstract":["<h4>Introduction</h4>RNA-binding proteins (RBPs) shape post-transcriptional programs in cancer, yet subtype-specific roles in breast cancer remain unclear. We evaluated whether CUGBP Elav-like family member 1 (CELF1), an RBPs with prognostic relevance in luminal A (ER-positive) breast cancer, drives malignant phenotypes via glycolytic reprogramming through glucose transporter 1 (GLUT1).<h4>Methods</h4>We surveyed 1,337 RBPs across TCGA to identify luminal A prognosis-related candidates using Cox models and random-forest ranking, then validated CELF1 biologically. Functional assays combined CELF1 knockdown in ER-positive cells (MCF7, T47D) and overexpression in HER2-positive cells (SKBR3, HCC1954), RNA-seq with differential expression and GSEA, qPCR,western blot, migration, colony assays, IHC in clinical tissues, and a nude-mouse xenograft with the GLUT1 inhibitor BAY-876.<h4>Results</h4>Cox and random-forest analyses prioritized CELF1 among prognosis-related RBPs in luminal A tumors; high CELF1 associated with poorer survival and was overexpressed in breast cancer versus normal tissue. CELF1 modulation bidirectionally altered glycolytic programs and malignant traits: CELF1 loss reduced proliferation, colony formation, migration, and xenograft growth, whereas overexpression enhanced these phenotypes. RNA-seq and enrichment analyses highlighted suppression of glycolysis pathways upon CELF1 loss; GLUT1 (SLC2A1), HK2, and G6PD were consistently downregulated at mRNA and protein levels after CELF1 knockdown and upregulated with CELF1 overexpression. In vivo, combining CELF1 knockout with BAY-876 further curtailed tumor growth and proliferation markers.<h4>Conclusion</h4>CELF1 promotes aerobic glycolysis and aggressive behavior in ER-positive breast cancer, at least partly by regulating GLUT1. These findings reveal RBP-driven metabolic reprogramming in luminal A disease and nominate the CELF1-GLUT1 axis as a potential therapeutic vulnerability."],"journal":["Frontiers in genetics"],"pagination":["1687066"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12646540"],"repository":["biostudies-literature"],"pubmed_title":["CELF1 promotes aerobic glycolysis and an aggressive phenotype in ER-positive breast cancer via GLUT1 regulation."],"pmcid":["PMC12646540"],"pubmed_authors":["Wang N","Guo M","Li J","Xu B","Huang G","Bi J"],"additional_accession":[]},"is_claimable":false,"name":"CELF1 promotes aerobic glycolysis and an aggressive phenotype in ER-positive breast cancer via GLUT1 regulation.","description":"<h4>Introduction</h4>RNA-binding proteins (RBPs) shape post-transcriptional programs in cancer, yet subtype-specific roles in breast cancer remain unclear. We evaluated whether CUGBP Elav-like family member 1 (CELF1), an RBPs with prognostic relevance in luminal A (ER-positive) breast cancer, drives malignant phenotypes via glycolytic reprogramming through glucose transporter 1 (GLUT1).<h4>Methods</h4>We surveyed 1,337 RBPs across TCGA to identify luminal A prognosis-related candidates using Cox models and random-forest ranking, then validated CELF1 biologically. Functional assays combined CELF1 knockdown in ER-positive cells (MCF7, T47D) and overexpression in HER2-positive cells (SKBR3, HCC1954), RNA-seq with differential expression and GSEA, qPCR,western blot, migration, colony assays, IHC in clinical tissues, and a nude-mouse xenograft with the GLUT1 inhibitor BAY-876.<h4>Results</h4>Cox and random-forest analyses prioritized CELF1 among prognosis-related RBPs in luminal A tumors; high CELF1 associated with poorer survival and was overexpressed in breast cancer versus normal tissue. CELF1 modulation bidirectionally altered glycolytic programs and malignant traits: CELF1 loss reduced proliferation, colony formation, migration, and xenograft growth, whereas overexpression enhanced these phenotypes. RNA-seq and enrichment analyses highlighted suppression of glycolysis pathways upon CELF1 loss; GLUT1 (SLC2A1), HK2, and G6PD were consistently downregulated at mRNA and protein levels after CELF1 knockdown and upregulated with CELF1 overexpression. In vivo, combining CELF1 knockout with BAY-876 further curtailed tumor growth and proliferation markers.<h4>Conclusion</h4>CELF1 promotes aerobic glycolysis and aggressive behavior in ER-positive breast cancer, at least partly by regulating GLUT1. These findings reveal RBP-driven metabolic reprogramming in luminal A disease and nominate the CELF1-GLUT1 axis as a potential therapeutic vulnerability.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025","modification":"2026-06-05T18:56:45.886Z","creation":"2026-05-20T03:14:02.016Z"},"accession":"S-EPMC12646540","cross_references":{"pubmed":["41306913"],"doi":["10.3389/fgene.2025.1687066"]}}