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mTOR signalling and cellular metabolism are mutual determinants in cancer

Nature Reviews Cancer volume 18, pages 744–757 (2018)Cite this article

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Abstract

Oncogenic signalling and metabolic alterations are interrelated in cancer cells. mTOR, which is frequently activated in cancer, controls cell growth and metabolism. mTOR signalling regulates amino acid, glucose, nucleotide, fatty acid and lipid metabolism. Conversely, metabolic inputs, such as amino acids, activate mTOR. In this Review, we discuss how mTOR signalling rewires cancer cell metabolism and delineate how changes in metabolism, in turn, sustain mTOR signalling and tumorigenicity. Several drugs are being developed to perturb cancer cell metabolism. However, their efficacy as stand-alone therapies, similar to mTOR inhibitors, is limited. Here, we discuss how the interdependence of mTOR signalling and metabolism can be exploited for cancer therapy.

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Fig. 1: Activation of mTOR signalling.
Fig. 2: mTOR-driven reprogramming of amino acid metabolism.
Fig. 3: mTOR controls glucose metabolism in cancer.
Fig. 4: Rewiring of nucleotide metabolism by mTOR.
Fig. 5: Regulation of fatty acid and lipid metabolism.

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Acknowledgements

D.M. acknowledges support from the German Research Foundation (DFG). M.N.H. acknowledges support from the European Research Council (ERC) (Mechanisms of Evasive Resistance in Cancer (MERiC)), SystemsX.CH, the Louis Jeantet Foundation and the Swiss National Science Foundation.

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Nature Reviews Cancer thanks the anonymous reviewers for their contribution to the peer review of this work.

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  1. Biozentrum, University of Basel, Basel, Switzerland

    Dirk Mossmann, Sujin Park & Michael N. Hall

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D.M. and S.P. researched data for the article, substantially contributed to the discussion of content, wrote the article and edited the manuscript before submission. M.N.H. substantially contributed to the discussion of content, wrote the article and edited the manuscript before submission.

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Correspondence to Michael N. Hall.

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Mossmann, D., Park, S. & Hall, M.N. mTOR signalling and cellular metabolism are mutual determinants in cancer. Nat Rev Cancer 18, 744–757 (2018). https://doi.org/10.1038/s41568-018-0074-8

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