Frataxin participates to the hypoxia-induced response in tumors

I. Guccini, D. Serio, I. Condò, A. Rufini, B. Tomassini, A. Mangiola, G. Maira, C. Anile, D. Fina, F. Pallone, M. P. Mongiardi, A. Levi, N. Ventura, R. Testi, F. Malisan

Research output: Contribution to journalArticle

Abstract

Defective expression of frataxin is responsible for the degenerative disease Friedreich's ataxia. Frataxin is a protein required for cell survival since complete knockout is lethal. Frataxin protects tumor cells against oxidative stress and apoptosis but also acts as a tumor suppressor. The molecular bases of this apparent paradox are missing. We therefore sought to investigate the pathways through which frataxin enhances stress resistance in tumor cells. We found that frataxin expression is upregulated in several tumor cell lines in response to hypoxic stress, a condition often associated with tumor progression. Moreover, frataxin upregulation in response to hypoxia is dependent on hypoxia-inducible factors expression and modulates the activation of the tumor-suppressor p53. Importantly, we show for the first time that frataxin is in fact increased in human tumors in vivo. These results show that frataxin participates to the hypoxia-induced stress response in tumors, thus implying that modulation of its expression could have a critical role in tumor cell survival and/or progression.

Original languageEnglish
Article numbere123
JournalCell Death and Disease
Volume2
Issue number2
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Neoplasms
Cell Survival
Friedreich Ataxia
frataxin
Hypoxia
Tumor Cell Line
Oxidative Stress
Up-Regulation
Apoptosis
Proteins

Keywords

  • Frataxin
  • Friedreich's ataxia
  • HIF
  • Hypoxia
  • p53
  • Tumor

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Guccini, I., Serio, D., Condò, I., Rufini, A., Tomassini, B., Mangiola, A., ... Malisan, F. (2011). Frataxin participates to the hypoxia-induced response in tumors. Cell Death and Disease, 2(2), [e123]. https://doi.org/10.1038/cddis.2011.5

Frataxin participates to the hypoxia-induced response in tumors. / Guccini, I.; Serio, D.; Condò, I.; Rufini, A.; Tomassini, B.; Mangiola, A.; Maira, G.; Anile, C.; Fina, D.; Pallone, F.; Mongiardi, M. P.; Levi, A.; Ventura, N.; Testi, R.; Malisan, F.

In: Cell Death and Disease, Vol. 2, No. 2, e123, 02.2011.

Research output: Contribution to journalArticle

Guccini, I, Serio, D, Condò, I, Rufini, A, Tomassini, B, Mangiola, A, Maira, G, Anile, C, Fina, D, Pallone, F, Mongiardi, MP, Levi, A, Ventura, N, Testi, R & Malisan, F 2011, 'Frataxin participates to the hypoxia-induced response in tumors', Cell Death and Disease, vol. 2, no. 2, e123. https://doi.org/10.1038/cddis.2011.5
Guccini I, Serio D, Condò I, Rufini A, Tomassini B, Mangiola A et al. Frataxin participates to the hypoxia-induced response in tumors. Cell Death and Disease. 2011 Feb;2(2). e123. https://doi.org/10.1038/cddis.2011.5
Guccini, I. ; Serio, D. ; Condò, I. ; Rufini, A. ; Tomassini, B. ; Mangiola, A. ; Maira, G. ; Anile, C. ; Fina, D. ; Pallone, F. ; Mongiardi, M. P. ; Levi, A. ; Ventura, N. ; Testi, R. ; Malisan, F. / Frataxin participates to the hypoxia-induced response in tumors. In: Cell Death and Disease. 2011 ; Vol. 2, No. 2.
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