CELF1 promotes aerobic glycolysis and an aggressive phenotype in ER-positive breast cancer via GLUT1 regulation

Introduction 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). Methods 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. Results 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. Conclusion 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.

• Publication year

  2025

• Venue

  Frontiers in Genetics

• Publication date

  2025-11-12

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fgene.2025.1687066PMID 41306913PMCID 12646540
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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