Research Papers:

FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration

Véronique Frattini, Federica Pisati, Maria Carmela Speranza, Pietro Luigi Poliani, Gianmaria Frigé, Gabriele Cantini, Dimos Kapetis, Manuela Cominelli, Alessandra Rossi, Gaetano Finocchiaro and Serena Pellegatta _

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Oncotarget. 2012; 3:1146-1157. https://doi.org/10.18632/oncotarget.644

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Véronique Frattini1,3, Federica Pisati1,3, Maria Carmela Speranza1,3, Pietro Luigi Poliani4, Gianmaria Frigé3, Gabriele Cantini1,3, Dimos Kapetis2, Manuela Cominelli4, Alessandra Rossi1,3, Gaetano Finocchiaro1,3 and Serena Pellegatta1,3

1 Unit of Molecular Neuro-Oncology, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Milan, Italy

2 Service of Bioinformatics, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Milan, Italy

3 Department of Experimental Oncology, European Institute of Oncology - Campus IFOM-IEO, Milan, Italy

4 Department of Pathology, University of Brescia, Brescia, Italy


Serena Pellegatta, email:

Gaetano Finocchiaro, email:

Keywords: FOXP3, glioblastoma, neurospheres, proliferation, migration

Received: September 03, 2012, Accepted: September 20, 2012, Published: September 22, 2012


The transcription factor FOXP3 plays an essential role in regulatory T cell development and function. In addition, it has recently been identified as a tumor suppressor in different cancers. Here, we report that FOXP3 is expressed in normal brain but strongly down-regulated in glioblastoma (GB) and in corresponding GB stem-like cells growing in culture as neurospheres (GB-NS), as evaluated by real time-PCR and confirmed by immunohistochemistry on an independent set of GB. FOXP3 expression was higher in low-grade gliomas than in GB. Interestingly, we also found that neurosphere generation, a feature present in 58% of the GB that we examined, correlated with lower expression of FOXP3 and shorter patient survival. FOXP3 silencing in one GB-NS expressing measurable levels of the gene caused a significant increase in proliferation and migration as well as highly aggressive growth in xenografts. Conversely, FOXP3 over-expression impaired GB-NS migration and proliferation in vitro.

We also demonstrated using ChiP that FOXP3 is a transcriptional regulator of p21 and c-MYC supporting the idea that dysregulated expression of these factors is a major mechanism of tumorigenesis driven by the loss of FOXP3 expression in gliomas. These findings support the assertion that FOXP3 exhibits tumor suppressor activity in glioblastomas.

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