FCGBP promotes malignant phenotypes of glioblastoma cells via activation of the TGF-β1 signaling pathway.

Objective

To investigate the expression level of IgG Fc-binding protein (FCGBP) in glioma cells, elucidate its role in malignant tumor phenotypes, and explore its relationship with the transforming growth factor-β (TGF-β) signaling pathway.

Methods

The expression of FCGBP was compared between primary human astrocytes (HA) and glioma cell lines (U87, U251, LN229, and T98G). FCGBP was then silenced in U87 cells. Cell proliferation, migration, and invasion were assessed using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation, wound healing, and Matrigel-coated Transwell assays. Apoptosis and cell-cycle distribution in U87 cells were analyzed by flow cytometry. Co-immunoprecipitation (Co-IP) was performed to validate the endogenous association between FCGBP and TGF-β1-containing protein complexes. Rescue experiments were conducted using recombinant TGF-β1 protein. Additionally, the in vitro findings were further validated in nude mouse xenograft models.

Results

FCGBP was highly expressed in various glioma cell lines, and its knockdown reduced TGF-β levels in the culture supernatant. Knockdown of FCGBP in U87 cells significantly suppressed malignant behaviors, including proliferation, migration, and invasion, while inducing apoptosis and cell-cycle arrest. Co-IP assays suggested an endogenous association between FCGBP and TGF-β1-containing protein complexes, and treatment with recombinant TGF-β1 effectively reversed the inhibitory effects of FCGBP knockdown. In vivo experiments confirmed that silencing FCGBP markedly inhibited tumor growth in nude mice and significantly reduced systemic inflammation and TGF-β levels.

Conclusion

FCGBP promotes malignant phenotypes in glioma cells (U87) and accelerates tumor growth in vivo, potentially through activation of the TGF-β/Smad signaling pathway.