FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration

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

Research output: Contribution to journalArticle

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 stronglydown-regulated in glioblastoma (GB) and in corresponding GB stem-like cells growing in culture as neurospheres (GB-NS), as evaluatedby real time-PCR and confirmed by immunohistochemistry on an independent set of GB. FOXP3 expression was higher in low-grade gliomasthan 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 genecaused 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.

Original languageEnglish
Pages (from-to)1146-1157
Number of pages12
JournalOncotarget
Volume3
Issue number10
Publication statusPublished - 2012

Keywords

  • FOXP3
  • Glioblastoma
  • Migration
  • Neurospheres
  • Proliferation

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Frattini, VJ. É., Pisati, F., Speranza, M. C., Poliani, P. L., Frigé, G., Cantini, G., Kapetis, D., Cominelli, M., Rossi, A., Finocchiaro, G., & Pellegatta, S. (2012). FOXP3, a novel glioblastoma oncosuppressor, affects proliferation and migration. Oncotarget, 3(10), 1146-1157.