488P - ITGA2 promotes glioma cell stemness and progression by activating the AKT pathway

Background

Glioma, the most common malignancy of the central nervous system, is charactarised by its extensive proliferation and invasion. An increasing number of studies suggest that glioma stem cells (GSCs) are at the root of glioma's difficulty in control, treatment and recurrence. The adhesion molecule integrin α2 (ITGA2) plays an important role in regulating various biological behaviors such as cell migration, growth and differentiation. Previous studies have shown that ITGA2 is closely associated with tumor progression, but the role and mechanism of ITGA2 in regulating glioma progression and stemness remain unclear.

Methods

The gene expression profile of GSCs was analyzed by RNA-seq. ITGA2 expression in glioma tissues was examined by immunohistochemical staining, followed by analysis of the correlation between ITGA2 expression and clinical features. In addition, the effects of lentivirus-mediated RNA interference of ITGA2 on cell proliferation, cell migration, spheroid forming ability and cell stemness specific gene and protein expression in glioma cells were investigated.

Results

The expression level of ITGA2 was significantly increased in GSCs compared to glioma cells. ITGA2 protein expression was increased in high-grade glioma samples. Prognostic analysis showed that patients with high ITGA2 expression had shorter survival. In glioma cells, knockdown of ITGA2 significantly inhibited the proliferation, migration, invasion and spheroid forming ability of glioma cells. TCGA data analysis showed that ITGA2 expression positively correlated with the expression of stem cell-specific genes in gliomas. Knockdown of ITGA2 significantly reduced the expression levels of stem cell-specific genes and proteins in the cells. The molecular mechanism revealed that ITGA2 knockdown inhibited the activation of the AKT signaling pathway. The AKT phosphorylation activator SC79 reversed the reduced sphere-forming ability of glioma cells and the reduced expression levels of stem cell-specific genes and proteins in cells caused by ITGA2 knockdown.

Conclusions

Our findings elucidate the role and molecular mechanism of ITGA2 in regulating glioma progression and stemness, and provide new ideas for basic glioma research and tumor treatment strategies targeting GSCs.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.