Annexin 2A sustains glioblastoma cell dissemination and proliferation

// Francesca Maule 1 , Silvia Bresolin 1 , Elena Rampazzo 1, 2 , Daniele Boso 1 , Alessandro Della Puppa 3 , Giovanni Esposito 4 , Elena Porcu 1 , StefaniaMitola 5 , Giuseppe Lombardi 6 , Benedetta Accordi 1 , Manuela Tumino 7 , Giuseppe Basso 1, 7 , Luca Persano 1, 2 1 Department of Woman and Child Health, University of Padova, Padova, IT 2 Istituto di Ricerca Pediatrica (IRP) – Citta della Speranza, Padova, IT 3 Neurosurgery Unit, University-Hospital of Padova, Padova, IT 4 Istituto Oncologico Veneto, IRCCS, Padova, IT 5 Experimental Oncology and Immunology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, IT 6 Department of Clinical and Experimental Oncology, Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, IT 7 Clinic of Pediatric Oncohematology, University-Hospital of Padova, Padova, IT Correspondence to: Luca Persano, email: luca.persano@unipd.it Keywords: annexin2A, glioblastoma, invasion, cell cycle, cytoskeletal remodeling Received: March 09, 2016 Accepted: June 03, 2016 Published: July 13, 2016 ABSTRACT Glioblastoma (GBM) is the most devastating tumor of the brain, characterized by an almost inevitable tendency to recur after intensive treatments and a fatal prognosis. Indeed, despite recent technical improvements in GBM surgery, the complete eradication of cancer cell disseminated outside the tumor mass still remains a crucial issue for glioma patients management. In this context, Annexin2A (ANXA2) is a phospholipid-binding protein expressed in a variety of cell types, whose expression has been recently associated with cell dissemination and metastasis in many cancer types, thus making ANXA2 an attractive putative regulator of cell invasion also in GBM. Here we show that ANXA2 is over-expressed in GBM and positively correlates with tumor aggressiveness and patient survival. In particular, we associate the expression of ANXA2 to a mesenchymal and metastatic phenotype of GBM tumors. Moreover, we functionally characterized the effects exerted by ANXA2 inhibition in primary GBM cultures, demonstrating its ability to sustain cell migration, matrix invasion, cytoskeletal remodeling and proliferation. Finally, we were able to generate an ANXA2-dependent gene signaturewith a significant prognostic potential in different cohorts of solid tumor patients, including GBM. In conclusion, we demonstrate that ANXA2 acts at multiple levels in determining the disseminating and aggressive behaviour of GBM cells, thus proving its potential as a possible target and strong prognostic factor in the future management of GBM patients.