Angi-04. ikip suppresses migration and invasion of glioblastoma by downregulating thbs1/fak signaling

Abstract BACKGROUND The role of the inhibitor of NF-κB kinase-interacting protein (IKIP) in glioblastoma (GBM) migration and invasion remains poorly understood, despite its known involvement in the negative regulation of NF-κB signaling and inflammation. This study aimed to investigate the impact of IKIP on GBM metastasis and elucidate the underlying molecular mechanisms. METHODS Expression levels of IKIP were analyzed in gliomas and normal brain tissues using bioinformatic analysis of public databases and immunohistochemical staining of clinical samples. Transwell and wound healing assays were employed to assess the migration and invasion of GBM cell lines. RNA sequencing was conducted to unravel the molecular pathways involved. RESULTS Bioinformatic analysis revealed a significantly higher expression of IKIP in GBM compared to normal brain tissues, and its upregulation was associated with a poor prognosis in glioma patients. However, immunohistochemical and immunofluorescent staining demonstrated the downregulation of IKIP in GBM. Furthermore, functional assays demonstrated that IKIP overexpression suppressed the migratory and invasive capabilities of GBM cell lines, whereas IKIP knockdown enhanced migration and invasion. Mechanistically, IKIP overexpression downregulated THBS1 at the transcriptional level, resulting in the inhibition of THBS1/FAK signaling. CONCLUSIONS This study provides evidence for the first time that IKIP exerts inhibitory effects on GBM migration and invasion by downregulating THBS1/FAK signaling. These findings shed light on the complex mechanisms underlying GBM progression and identify IKIP as a potential therapeutic target for GBM invasion.