Abstract
Glioblastoma multiform (GBM) constitutes approximately 14.7 % of all central nervous system tumors (CNSTs) and 45.2 % of primary malignant CNSTs. Extensive research has indicated that β-arrestin 1 (ARRB1) plays a significant role in tumor malignancy. In this investigation, we established GBM cell lines representing normal control (NC), overexpression (OE) and Δexon13 GBM variants (△exon13) of ARRB1. Our findings indicate that the ARRB1-OE isoform facilitated GBM cell proliferation and migration, with the ARRB1-△exon13 isoform further augmenting this effect. Notably, the isoform ARRB1-△exon13 binds to glycolytic proteins including ENO1 and ALDOA and regulates glycolysis. In vivo studies corroborate the tumor-promoting effects of ARRB1-Δexon13. Furthermore, we demonstrate that 2-DG effectively inhibits the malignancy-promoting capabilities of ARRB1-Δexon13 by reducing pyruvate levels. Our identification of alternative RNA splicing events of ARRB1 reveals a mechanism by which GBM cell malignancy is augmented through ARRB1-Δexon13, which mediates glycolysis-related pathways.