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mTORC1 and mTORC2 in cancer and the tumor microenvironment

Oncogene volume 36, pages 2191–2201 (2017)Cite this article

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Abstract

The mammalian target of rapamycin (mTOR) is a crucial signaling node that integrates environmental cues to regulate cell survival, proliferation and metabolism, and is often deregulated in human cancer. mTOR kinase acts in two functionally distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), whose activities and substrate specificities are regulated by complex co-factors. Deregulation of this centralized signaling pathway has been associated with a variety of human diseases including diabetes, neurodegeneration and cancer. Although mTORC1 signaling has been extensively studied in cancer, recent discoveries indicate a subset of human cancers harboring amplifications in mTORC2-specific genes as the only actionable genomic alterations, suggesting a distinct role for mTORC2 in cancer as well. This review will summarize recent advances in dissecting the relative contributions of mTORC1 versus mTORC2 in cancer, their role in tumor-associated blood vessels and tumor immunity, and provide an update on mTOR inhibitors.

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Acknowledgements

We thank Deanna Edwards for careful review of the manuscript. This work was supported by the Department of Veterans Affairs through a VA Merit Award and a Research Career Scientist Award (J Chen), NIH grants R01 CA95004 and R01 CA177681 (J Chen) and T-32 CA009592 (L Kim).

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Authors and Affiliations

  1. Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA

    L C Kim, R S Cook & J Chen

  2. Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA

    R S Cook & J Chen

  3. Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University, Nashville, TN, USA

    J Chen

  4. Department of Cell & Developmental Biology, Vanderbilt University, Nashville, TN, USA

    J Chen

  5. Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA

    J Chen

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  1. L C Kim
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Correspondence to J Chen.

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Kim, L., Cook, R. & Chen, J. mTORC1 and mTORC2 in cancer and the tumor microenvironment. Oncogene 36, 2191–2201 (2017). https://doi.org/10.1038/onc.2016.363

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