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.

1. Dulbecco Laboratory for Cancer Research, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, California 9203, USA.
   Email: shaw@salk.edu
2. Department of Systems Biology, Harvard Medical School, and Division of Signal Transduction, Beth Israel Deaconess Medical Center, 300 Brookline Avenue, Boston, Massachusetts 02215, USA.
   Email: lcantley@hms.harvard.edu

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