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mTOR as a Positive Regulator of Tumor Cell Responses to Hypoxia

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TOR

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 279))

Abstract

Rapamycin is a clinically approved immunosuppressive agent that has recently shown promising antitumor activities in human patients. In contrast to many conventional chemotherapeutic agents, rapamycin displays a remarkably high level of selectivity for certain types of tumors. The pharmacological activities of rapamycin are attributable to the functional inhibition of a single target protein, termed the mammalian target of rapamycin (mTOR). Because mTOR is widely expressed in both normal and transformed cells, variations in mTOR expression levels are likely not a primary determinant of tumor sensitivity to rapamycin. However, recent studies highlighted an intriguing link between cancer cell sensitivity to rapamycin and deregulated signaling through the phosphoinositide (PI) 3-kinase pathway. These findings have prompted a search for cancer-related responses that are jointly regulated by the PI 3-kinase signaling cascade and mTOR. The oxygen-regulated transcription factor, hypoxia-induced factor (HIF)-1, has emerged as a candidate target for both of these two highly interactive signaling proteins. Here we review evidence that mTOR functions as a positive regulator of HIF-1-dependent responses to hypoxic stress in human cancer cells.

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  1. Program in Signal Transduction Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA

    R. T. Abraham

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  1. R. T. Abraham
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  1. Friedrich-Miescher-Institute, Maulbeerstrasse 66, 4058, Basel, Switzerland

    George Thomas

  2. Whitehead Institute, 9 Cambridge Center, Cambridge, MA, 02142, USA

    David M. Sabatini MD, PhD

  3. Biozentrum, University of Basel, Klingelbergstrasse 70, 4056, Basel, Switzerland

    Michael N. Hall

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Abraham, R.T. (2004). mTOR as a Positive Regulator of Tumor Cell Responses to Hypoxia. In: Thomas, G., Sabatini, D.M., Hall, M.N. (eds) TOR. Current Topics in Microbiology and Immunology, vol 279. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18930-2_18

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  • DOI: https://doi.org/10.1007/978-3-642-18930-2_18

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62360-8

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