ITGA5 drives glioblastoma progression through SLK-mediated activation of the PI3K-Akt pathway.

Abstract

Glioblastoma (GBM) is the most common type of malignant primary brain tumor and exhibits a rising trend in both incidence and mortality rates. Several studies have shown Integrin Subunit Alpha 5 (ITGA5) has oncogene-promoting functions in GBM, but its underlying mechanisms remain unclear. Based on public high-throughput RNA sequencing data, we found ITGA5 expression is upregulated in GBM tissues and cells, which was correlated with poor prognosis and pathological parameters. Next, the experiments further demonstrated that ITGA5 promotes GBM in vitro and in vivo. The potential mechanism of ITGA5 in GBM was investigated by proteomics and phosphoproteomics sequencing, and the PI3K-Akt signaling pathway were mainly enriched after knockdown of ITGA5. As a downstream gene of the PI3K-Akt pathway, we proved elevated ITGA5promote GBM cell invasion and migration through SLK. Finally, the expression of ITGA5 and SLK in malignant astrocytes of different states in GBM patients showed heterogeneity using single-cell sequencing. Overall, our findings highlight a novel molecular mechanism for the tumorigenesis driven by upregulated ITGA5 in GBM, suggesting that the ITGA5-SLK axis may be a new therapeutic target for the treatment of GBM.