Oncotarget

Research Papers:

FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration

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

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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 _

Abstract

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

Correspondence:

Serena Pellegatta, email:

Gaetano Finocchiaro, email:

Keywords: FOXP3, glioblastoma, neurospheres, proliferation, migration

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

Abstract

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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