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  • Original Article
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Ras-dependent carbon metabolism and transformation in mouse fibroblasts

Oncogene volume 25, pages 5391–5404 (2006)Cite this article

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.

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Acknowledgements

We thank Chiara Magnani for technical assistance and discussion. This work has been supported by grants to LA (AIRC, Cariplo and MIUR-Progetto Strategico Oncologia) and to MV (MIUR). ES has been supported by a fellowship from FIRC.

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Authors and Affiliations

  1. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy

    F Chiaradonna, E Sacco, R Manzoni, M Vanoni & L Alberghina

  2. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy

    M Giorgio

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  1. F Chiaradonna
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  2. E Sacco
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  3. R Manzoni
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  4. M Giorgio
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  5. M Vanoni
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  6. L Alberghina
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Correspondence to L Alberghina.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Chiaradonna, F., Sacco, E., Manzoni, R. et al. Ras-dependent carbon metabolism and transformation in mouse fibroblasts. Oncogene 25, 5391–5404 (2006). https://doi.org/10.1038/sj.onc.1209528

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