Upregulation of the canonical signaling pathway of interferon-gamma is associated with glioblastoma progression

Background Glioblastoma is a brain malignant tumor grade IV, highly invasive. Alterations in several signaling pathways are involved in glioblastoma development. In this work, we evaluated the IFN-gamma canonical signaling pathway in glioblastoma cells and its effect on cell viability and migration.Methods The levels of STAT1/pSTAT1, IRF1, and PD-L1 in LN-18 glioblastoma cells were analyzed using western blotting. Cell viability was evaluated by calcein-AM/propidium iodide assays, and a wound healing assay was used to study the migration of glioblastoma cells treated with IFN-gamma. Our aim was to determine the expression of IFN-gamma signaling elements in cell lines and tissue from glioblastoma samples and examine the relationship between these elements and the survival of glioblastoma patients. The following platforms were utilized for analysis: the CCLE (Cancer Cell Line Encyclopedia), UALCAN (University of Alabama at Birmingham Cancer data analysis Portal), GEPIA (Gene Expression Profiling Interactive Analysis), and GENT2 (Gene Expression patterns across Normal and Tumor tissues).Results Our results evidenced that IFN-gamma signaling increases non-phosphorylated and phosphorylated STAT1 levels and promotes the upregulation of IRF1 and PD-L1 in glioblastoma cells. The activation of IFN-gamma signaling increased cell migration without affecting the viability of glioblastoma cells. Furthermore, in silico analysis showed that the elements of IFN-gamma signaling pathways (IFNGR1/IFNGR2/STAT1/IRF1) are upregulated in human glioblastoma samples. The upregulation of IFN-gamma signaling was associated with shorter survival in glioblastoma patients.Conclusion IFN-gamma signaling pathway is upregulated in glioblastoma, displaying pro-tumor activity. Thus, IFN-gamma signaling elements may be potential biomarkers and targets for treating glioblastoma.