ITGA5 induces mesenchymal transformation to promote gliomas progression via PI3K/AKT/mTORC1 signaling pathway

Glioma is a common malignant tumor of the central nervous system, characterized by high malignancy, strong invasiveness and high recurrence rate. Integrin α5 (ITGA5), a member of the Integrin adhesion molecule family, has been reported to be associated with tumor progression and metastasis. In this study, we first identified the overexpression of ITGA5 in glioma through bioinformatics analysis. Kaplan-Meier analysis, COX regression analysis, and nomogram modeling revealed that high ITGA5 expression was significantly associated with poor prognosis in glioma patients. The ssGSEA showed that the high expression of ITGA5 had a higher level of immune cell infiltration, especially aDCs, B cells, CD8 + T cells, Macrophages, T helper cells, etc. To validate the results of bioinformatics analysis, we used qRT-PCR and Western blot assay confirmed that ITGA5 expression was up-regulated in glioma tissues and increased with pathological grade. Immunohistochemistry showed that high expression of ITGA5 was positively correlated with WHO grade, Ki67 expression and P53 status (P < 0.05). Univariate and multivariate COX regression analysis showed that ITGA5 expression was an independent prognostic marker in gliomas. Functionally, silencing of ITGA5 significantly inhibited the proliferation, invasion, and migration of glioma cells. The GSEA analysis indicated that ITGA5 was involved in mesenchymal transformation, PI3K/Akt/mTORC1 pathways. In vitro experiments further confirmed that ITGA5 positively regulates mesenchymal transformation and activates the PI3K/Akt/mTORC1 pathway. Moreover, treatment with PI3K Activator 740Y-P was able to reverse the effects of ITGA5 silencing on glioma cells growth and mesenchymal transformation. Therefore, ITGA5 may be a potential therapeutic target for the individualized treatment of glioma patients.

Bioinformatics; Glioma; Integrin α5; Prognosis; Proliferation.