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Ras, PI(3)K and mTOR signalling controls tumour cell growth

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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Figure 1: Ancient growth-control pathways.
Figure 2: Pathway circuitry dictates therapeutic response.

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Acknowledgements

We thank K. Cichowski, K. Lamia and J. Blenis for critical reading of the manuscript, and we apologize to many colleagues whose work could only be cited indirectly because of space limitations.

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Shaw, R., Cantley, L. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 441, 424–430 (2006). https://doi.org/10.1038/nature04869

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