Annexin 2A sustains glioblastoma cell dissemination and proliferation affecting patient prognosis

Glioblastoma (GBM) is the most devastating tumour of the brain, endowed with a fatal prognosis. Indeed, the complete eradication of cancer cell disseminated outside the GBM mass still remains a crucial issue. Given the reported strong association existing between Annexin 2A (ANXA2) expression and cell dissemination in many cancers, we evaluated the effects exerted by the modulation of ANXA2 levels in GBM cells and assessed its potential in predicting patient outcome. Here, we show that expression of ANXA2 positively correlates with metastatic gene signatures and demonstrates to be prognostic by itself. Indeed, we prove that ANXA2 is involved in cell migration, invasion, cytoskeletal remodeling and proliferation in GBM cells. Moreover, we were able to construct a gene signature representative of ANXA2 inhibition, which showed a significant prognostic potential in different GBM patient cohorts. In this study, we demonstrate that ANXA2 acts at multiple levels in determining the disseminating and aggressive behaviour of GBM tumours. In particular, we clearly show that ANXA2 is involved in determining a migrating and disseminating phenotype of GBM cells, in controlling specific cell cycle checkpoints and a cytoskeletal remodeling associated to cell movement. These data sustain the potential of ANXA2 as a possible target and strong prognostic factor in the future management of GBM patients. Gene expression was measured on Affymetrix in 4 independent experiments of primary GBM cells treated with an ANXA2 neutralizing antibody