FGFR4 Enhances Extracellular Vesicle-Associated Output and Promotes STAT1-Dependent LGALS3BP Enrichment in Colorectal Cancer

Fibroblast growth factor receptor 4 (FGFR4) contributes to colorectal cancer (CRC) progression, but its effects on extracellular vesicle (EV)-associated proteins remain unclear. In the present study, we examined FGFR4-associated changes in EV-enriched extracellular fractions and the role of STAT1 in LGALS3BP regulation.

EV-enriched fractions from conditioned media of CT26-vector and CT26-FGFR4 cells were analyzed by nanoparticle tracking analysis and liquid chromatography-tandem mass spectrometry. Proteomic findings were integrated with RNA-sequencing and STAT1-related chromatin immunoprecipitation-sequencing and perturbation datasets. STAT1 dependence was examined using siRNA knockdown, quantitative real-time PCR, and immunoblotting. Associations among FGFR4, STAT1, and LGALS3BP were assessed in the CNUHH CRC cohort and TCGA COAD/READ datasets.

Particle concentration and size did not differ significantly between CT26-vector and CT26-FGFR4 preparations. Proteomic analysis detected 736 proteins, including 36 previously annotated in EV/exosome databases. LGALS3BP, MFGE8, and AXL were selected as extracellular candidates, and LGALS3BP was also identified in the filtered STAT1-associated transcriptional signature. FGFR4 overexpression increased the expression of interferon-responsive genes, including Lgals3bp, and was accompanied by higher LGALS3BP, TSG101, and ALIX abundance in EV-enriched fractions. STAT1 knockdown attenuated Lgals3bp mRNA induction and reduced LGALS3BP abundance in these fractions without comparable reductions in TSG101 or ALIX. In the CNUHH and TCGA cohorts, LGALS3BP expression was positively correlated with FGFR4 and STAT1, although stage-specific patterns differed.

FGFR4 overexpression was associated with altered protein composition in EV-enriched extracellular fractions and STAT1-dependent LGALS3BP induction. These findings identify the FGFR4-STAT1-LGALS3BP relationship as a component of extracellular remodeling in CRC.

Abstract from PubMed (PMID 42966629). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.