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.
| Original language | English |
|---|---|
| Pages (from-to) | 54632-54649 |
| Number of pages | 18 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 34 |
| DOIs | |
| Publication status | Published - 2016 |
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Keywords
- Annexin 2A
- Cell cycle
- Cytoskeletal remodeling
- Glioblastoma
- Invasion
ASJC Scopus subject areas
- Oncology
Cite this
Annexin 2A sustains glioblastoma cell dissemination and proliferation. / Maule, Francesca; Bresolin, Silvia; Rampazzo, Elena; Boso, Daniele; Della Puppa, Alessandro; Esposito, Giovanni; Porcù, Elena; Mitola, Stefania; Lombardi, Giuseppe; Accordi, Benedetta; Tumino, Manuela; Basso, Giuseppe; Persano, Luca.
In: Oncotarget, Vol. 7, No. 34, 2016, p. 54632-54649.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Annexin 2A sustains glioblastoma cell dissemination and proliferation
AU - Maule, Francesca
AU - Bresolin, Silvia
AU - Rampazzo, Elena
AU - Boso, Daniele
AU - Della Puppa, Alessandro
AU - Esposito, Giovanni
AU - Porcù, Elena
AU - Mitola, Stefania
AU - Lombardi, Giuseppe
AU - Accordi, Benedetta
AU - Tumino, Manuela
AU - Basso, Giuseppe
AU - Persano, Luca
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Annexin 2A
KW - Cell cycle
KW - Cytoskeletal remodeling
KW - Glioblastoma
KW - Invasion
UR - http://www.scopus.com/inward/record.url?scp=84983508980&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84983508980&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.10565
DO - 10.18632/oncotarget.10565
M3 - Article
AN - SCOPUS:84983508980
VL - 7
SP - 54632
EP - 54649
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 34
ER -