Ras-dependent carbon metabolism and transformation in mouse fibroblasts

F. Chiaradonna, E. Sacco, R. Manzoni, M. Giorgio, M. Vanoni, L. Alberghina

Research output: Contribution to journalArticle

Abstract

Mutational activation of ras genes is required for the onset and maintenance of different malignancies. Here we show, using a combination of molecular physiology, nutritional perturbations and transcriptional profiling, that full penetrance of phenotypes related to oncogenic Ras activation, including the shift of carbon metabolism towards fermentation and upregulation of key cell cycle regulators, is dependent upon glucose availability. These responses are induced by Ras activation, being specifically reverted by downregulation of the Ras pathway obtained through the expression of a dominant-negative Ras-specific guanine nucleotide exchange protein. Our data allow to link directly to ras activation the alteration in energy metabolism of cancer cells, their fragility towards glucose shortage and ensuing apoptotic death.

Original languageEnglish
Pages (from-to)5391-5404
Number of pages14
JournalOncogene
Volume25
Issue number39
DOIs
Publication statusPublished - Aug 31 2006

Fingerprint

Carbon
Nutritional Physiological Phenomena
Fibroblasts
Glucose
Guanine Nucleotides
ras Genes
Penetrance
Energy Metabolism
Fermentation
Neoplasms
Cell Cycle
Up-Regulation
Down-Regulation
Maintenance
Phenotype
Proteins

Keywords

  • Apoptosis
  • Cell cycle
  • Glucose metabolism
  • Ras
  • Transformed cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Chiaradonna, F., Sacco, E., Manzoni, R., Giorgio, M., Vanoni, M., & Alberghina, L. (2006). Ras-dependent carbon metabolism and transformation in mouse fibroblasts. Oncogene, 25(39), 5391-5404. https://doi.org/10.1038/sj.onc.1209528

Ras-dependent carbon metabolism and transformation in mouse fibroblasts. / Chiaradonna, F.; Sacco, E.; Manzoni, R.; Giorgio, M.; Vanoni, M.; Alberghina, L.

In: Oncogene, Vol. 25, No. 39, 31.08.2006, p. 5391-5404.

Research output: Contribution to journalArticle

Chiaradonna, F, Sacco, E, Manzoni, R, Giorgio, M, Vanoni, M & Alberghina, L 2006, 'Ras-dependent carbon metabolism and transformation in mouse fibroblasts', Oncogene, vol. 25, no. 39, pp. 5391-5404. https://doi.org/10.1038/sj.onc.1209528
Chiaradonna F, Sacco E, Manzoni R, Giorgio M, Vanoni M, Alberghina L. Ras-dependent carbon metabolism and transformation in mouse fibroblasts. Oncogene. 2006 Aug 31;25(39):5391-5404. https://doi.org/10.1038/sj.onc.1209528
Chiaradonna, F. ; Sacco, E. ; Manzoni, R. ; Giorgio, M. ; Vanoni, M. ; Alberghina, L. / Ras-dependent carbon metabolism and transformation in mouse fibroblasts. In: Oncogene. 2006 ; Vol. 25, No. 39. pp. 5391-5404.
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