FGFR4 Enhances Extracellular Vesicle-Associated Output and Promotes STAT1-Dependent LGALS3BP Enrichment in Colorectal Cancer
- 1Department of Internal Medicine, Division of Hematology and Oncology, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Republic of Korea
Abstract
Background/Aim: 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.
Materials and Methods: 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.
Results: 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.
Conclusion: 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.
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BibTeX
@article{daehwan2026fgfr4,
title = {{FGFR4 Enhances Extracellular Vesicle-Associated Output and Promotes STAT1-Dependent LGALS3BP Enrichment in Colorectal Cancer}},
author = {DAE-HWAN KIM and JI-NA CHOI and JUN EUL HWANG and HYUN JEONG SHIM and HYUN JIN BANG and HYEON‑JONG KIM and IK-JOO CHUNG and SANG-HEE CHO},
journal = {Cancer Genomics \& Proteomics},
year = {2026},
month = oct,
doi = {10.21873/cgp.20622},
url = {https://doi.org/10.21873/cgp.20622},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - FGFR4 Enhances Extracellular Vesicle-Associated Output and Promotes STAT1-Dependent LGALS3BP Enrichment in Colorectal Cancer
AU - DAE-HWAN KIM
AU - JI-NA CHOI
AU - JUN EUL HWANG
AU - HYUN JEONG SHIM
AU - HYUN JIN BANG
AU - HYEON‑JONG KIM
AU - IK-JOO CHUNG
AU - SANG-HEE CHO
PY - 2026
DA - 2026/10/31
JO - Cancer Genomics & Proteomics
DO - 10.21873/cgp.20622
UR - https://doi.org/10.21873/cgp.20622
AB - Background/Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.
SN - 1109-6535
SN - 1790-6245
ER -