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An activated mTOR mutant supports growth factor-independent, nutrient-dependent cell survival

Oncogene volume 23, pages 5654–5663 (2004)Cite this article

Abstract

In yeast, TOR couples cellular growth and metabolism to the availability of extracellular nutrients. In contrast, mammalian TOR kinase activity has been reported to be regulated by growth factor stimulation via the PI3K/Akt pathway. Consistent with this, growth factor deprivation results in dephosphorylation of the mTOR target proteins p70S6k and 4EBP1 in the face of abundant extracellular nutrients. To determine whether the activation of mTOR was sufficient to support cell survival in the absence of other growth factor-mediated signal transduction, we evaluated the ability of a growth factor-independent mTOR mutant, ΔTOR, to protect cells from growth factor deprivation. ΔTOR- but not wild-type mTOR-expressing cells were protected from many of the sequelae of growth factor deprivation including amino-acid transporter degradation, reduction of the glycolytic rate, cellular atrophy, decreased mitochondrial membrane potential, and Bax activation. Furthermore, ΔTOR expression increased growth factor-independent, nutrient-dependent cell survival and enhanced the ability of p53−/− MEFs to form colonies in soft agar. These results suggest that activating mutations of mTOR can contribute to apoptotic resistance and might contribute to cellular transformation.

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Acknowledgements

We thank Dr Bob Abraham for providing the mTOR/ΔTOR constructs and for helpful advice throughout the project, all the members of the Thompson lab for providing both criticism and support, and Trevor Hoffman for scoring the soft agar assays and for helpful discussions. ALE was supported by a fellowship from the Helen Hay Whitney Foundation. CBT was supported in part by grants from the NCI.

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  1. Abramson Family Cancer Research Institute, University of Pennsylvania, 450 BRB II/III, 421 Curie Blvd, Philadelphia, 19104, PA, USA

    Aimee L Edinger & Craig B Thompson

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  1. Aimee L Edinger
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  2. Craig B Thompson
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Correspondence to Craig B Thompson.

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Edinger, A., Thompson, C. An activated mTOR mutant supports growth factor-independent, nutrient-dependent cell survival. Oncogene 23, 5654–5663 (2004). https://doi.org/10.1038/sj.onc.1207738

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