title: Annexin 2A sustains glioblastoma cell dissemination and proliferation.
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, Annexin 2A (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 signature with 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.
authors.affiliation: Department of Woman and Child Health, University of Padova, Padova, IT.
authors.forename: Francesca
authors.initials: F
authors.lastname: Maule
authors.affiliation: Department of Woman and Child Health, University of Padova, Padova, IT.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bresolin
authors.affiliation: Department of Woman and Child Health, University of Padova, Padova, IT.|Istituto di Ricerca Pediatrica (IRP) - Città della Speranza, Padova, IT.
authors.forename: Elena
authors.initials: E
authors.lastname: Rampazzo
authors.affiliation: Department of Woman and Child Health, University of Padova, Padova, IT.
authors.forename: Daniele
authors.initials: D
authors.lastname: Boso
authors.affiliation: Neurosurgery Unit, University-Hospital of Padova, Padova, IT.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Della Puppa
authors.affiliation: Istituto Oncologico Veneto, IRCCS, Padova, IT.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.affiliation: Department of Woman and Child Health, University of Padova, Padova, IT.
authors.forename: Elena
authors.initials: E
authors.lastname: Porcù
authors.affiliation: Experimental Oncology and Immunology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, IT.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mitola
authors.affiliation: Department of Clinical and Experimental Oncology, Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, IT.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lombardi
authors.affiliation: Department of Woman and Child Health, University of Padova, Padova, IT.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Accordi
authors.affiliation: Clinic of Pediatric Oncohematology, University-Hospital of Padova, Padova, IT.
authors.forename: Manuela
authors.initials: M
authors.lastname: Tumino
authors.affiliation: Department of Woman and Child Health, University of Padova, Padova, IT.|Clinic of Pediatric Oncohematology, University-Hospital of Padova, Padova, IT.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.affiliation: Department of Woman and Child Health, University of Padova, Padova, IT.|Istituto di Ricerca Pediatrica (IRP) - Città della Speranza, Padova, IT.
authors.forename: Luca
authors.initials: L
authors.lastname: Persano
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017306:Annexin A2 / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness
chemical_list: D017306:Annexin A2
keywords: annexin 2A; cell cycle; cytoskeletal remodeling; glioblastoma; invasion