Transforming growth factor-β signaling in cancer invasion and metastasis

Authors

  • Suvi-Katri Leivonen,

    1. Department of Dermatology, University of Turku, FI-20521 Turku, Finland
    2. Department of Medical Biochemistry and Molecular Biology, University of Turku, FI-20520 Turku, Finland
    3. MediCity Research Laboratory, University of Turku, FI-20520 Turku, Finland
    Current affiliation:
    1. VTT Medical Biotechnology, FI-20520 Turku, Finland
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  • Veli-Matti Kähäri

    Corresponding author
    1. Department of Dermatology, University of Turku, FI-20521 Turku, Finland
    2. Department of Medical Biochemistry and Molecular Biology, University of Turku, FI-20520 Turku, Finland
    3. MediCity Research Laboratory, University of Turku, FI-20520 Turku, Finland
    • Department of Dermatology, University of Turku, P.O.B. 52, FI-20521 Turku, Finland
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Abstract

Transforming growth factor-β (TGF-β) family members are polypeptides with dual tumor suppressive and oncogenic effects. They signal through serine/threonine kinase receptor complexes, which phosphorylate cytoplasmic mediators, the Smads. Upon phosphorylation, Smads translocate to the nucleus and associate with transcriptional coactivators or corepressors, and regulate the transcriptional activation of various TGF-β responsive genes. In addition, TGF-β activates cellular mitogen-activated protein kinase signaling pathways, which crosstalk with Smad signaling and regulate growth, survival and motility of cells. During tumorigenesis, malignantly transformed cells often lose the response to the tumor suppressive effects of TGF-β, which, in turn, starts to act as an autocrine tumor promoting factor by enhancing cancer invasion and metastasis. In this review, we summarize current view on the role of TGF-β signaling in tumorigenesis, with emphasis on cancer invasion and metastasis. On the basis of these recent observations, we discuss new therapeutic strategies targeting TGF-β signaling at distinct levels as a basis for inhibiting tumor growth, angiogenesis, invasion and metastasis. © 2007 Wiley-Liss, Inc.

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