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Nature 441, 424-430 (25 May 2006) | doi:10.1038/nature04869; Published online 24 May 2006
Review article Ras, PI(3)K and mTOR signalling controls tumour cell growth
Reuben J. Shaw1 & Lewis C. Cantley2
Abstract
All eukaryotic cells coordinate cell growth with the availability of nutrients in their environment. The mTOR protein kinase has emerged as a critical growth-control node, receiving stimulatory signals from Ras and phosphatidylinositol-3-OH kinase (PI(3)K) downstream from growth factors, as well as nutrient inputs in the form of amino-acid, glucose and oxygen availability. Notably, components of the Ras and PI(3)K signalling pathways are mutated in most human cancers. The preponderance of mutations in these interconnected pathways suggests that the loss of growth-control checkpoints and promotion of cell survival in nutrient-limited conditions may be an obligate event in tumorigenesis.
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