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. © 2006 Nature Publishing Group. All rights reserved.

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 [10.1038/sj.onc.1209528].

Ras-dependent carbon metabolism and transformation in mouse fibroblasts

CHIARADONNA, FERDINANDO;SACCO, ELENA;VANONI, MARCO ERCOLE;ALBERGHINA, LILIA
2006

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. © 2006 Nature Publishing Group. All rights reserved.
Articolo in rivista - Articolo scientifico
Ras-dependent carbon metabolism
English
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 [10.1038/sj.onc.1209528].
Chiaradonna, F; Sacco, E; Manzoni, R; Giorgio, M; Vanoni, M; Alberghina, L
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/3654
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