High nuclear level of Vav1 is a positive prognostic factor in early invasive breast tumors: a role in modulating genes related to the efficiency of metastatic process
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Silvia Grassilli1,*, Federica Brugnoli1,*, Rossano Lattanzio2,3, Cosmo Rossi3,4, Letizia Perracchio5, Marcella Mottolese5, Marco Marchisio3,4, Maria Palomba1, Ervin Nika1, Pier Giorgio Natali6, Mauro Piantelli2,3, Silvano Capitani1,7 and Valeria Bertagnolo1
1 Section of Anatomy and Histology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
2 Department of Experimental and Clinical Sciences, University “G. d’Annunzio” Chieti, Italy
3 Center of Excellence for Research on Aging, Foundation University “G. d’Annunzio”, Chieti, Italy
4 Department of Biomorphology, University “G. D’Annunzio” Chieti, Italy
5 ‘‘Regina Elena’’ Cancer Institute, Rome, Italy
6 CINBO Laboratories, University ‘‘G. D’Annunzio’’, Chieti, Italy
7 LTTA Centre, University of Ferrara, Ferrara, Italy
* These authors contributed equally to this work
Silvano Capitani, email:
Valeria Bertagnolo, email:
Keywords: breast cancer; Vav1; cell nucleus; metastasis
Received: January 28, 2014 Accepted: May 25, 2014 Published: May 25, 2014
Vav1 is one of the signalling proteins normally restricted to hematopoietic cells that results ectopically expressed in solid tumors, including breast cancer. By immunohistochemical analysis on TMAs containing invasive breast tumor from patients without lymph node involvement, we have found that Vav1 is expressed in almost all investigated cancers and shows a peculiar localization inside the nucleus of tumor cells. High amounts of nuclear Vav1 are positively correlated with low incidence of relapse, regardless phenotype and molecular subtype of breast neoplasia. In particular, Kaplan-Meier plots showed an elevated risk of distant metastasis in patients with low Vav1 expression compared with patients with high Vav1 expression in their tumors. Experiments performed with breast tumor-derived cells indicated that Vav1 negatively modulates their invasiveness in vitro and their metastatic efficiency in vivo, possibly by affecting the expression of genes involved in invasion and/or metastasis of breast tumors. Since the high heterogeneity of breast tumors makes difficult to predict the evolution of early breast neoplasias, the evaluation of nuclear Vav1 levels may help in the characterization and management of early breast cancer patients. In particular, Vav1 may serve as a prognostic biomarker and a target for new therapies aimed to prevent breast cancer progression.
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