The dynamic roles of TGF-β in cancer

Authors

  • Erik Meulmeester,

    1. Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Postbus 9600, 2300 RC, Leiden, The Netherlands
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  • Peter ten Dijke

    Corresponding author
    1. Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Postbus 9600, 2300 RC, Leiden, The Netherlands
    2. Uppsala University and Ludwig Institute for Cancer Research, Box 595, 75124, Uppsala, Sweden
    • Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Building 2, Room R-02-022, Postzone S-1-P, Postbus 9600, 2300 RC, Leiden, The Netherlands.
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  • No conflicts of interest were declared.

Abstract

The transforming growth factor-β (TGF-β) signalling pathway plays a critical and dual role in the progression of human cancer. During the early phase of tumour progression, TGF-β acts as a tumour suppressor, exemplified by deletions or mutations in the core components of the TGF-β signalling pathway. On the contrary, TGF-β also promotes processes that support tumour progression such as tumour cell invasion, dissemination, and immune evasion. Consequently, the functional outcome of the TGF-β response is strongly context-dependent including cell, tissue, and cancer type. In this review, we describe the molecular signalling pathways employed by TGF-β in cancer and how these, when perturbed, may lead to the development of cancer. Concomitantly with our increased appreciation of the molecular mechanisms that govern TGF-β signalling, the potential to therapeutically target specific oncogenic sub-arms of the TGF-β pathway increases. Indeed, clinical trials with systemic TGF-β signalling inhibitors for treatment of cancer patients have been initiated. However, considering the important role of TGF-β in cardiovascular and many other tissues, careful screening of patients is warranted to minimize unwanted on-target side effects. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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