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TGF-β in Skin Cancer and Fibrosis

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TGF-β in Human Disease

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Abstract

Among all three isoforms of the TGF-β ligand, TGF-β1 is the predominant isoform in the skin. In normal skin, canonical TGF-β signaling components, i.e., TGF-β receptors and signaling Smads, are broadly and highly expressed, whereas TGF-β ligands are expressed at very low levels. These expression patterns determine that the TGF-β signaling input to the skin is low under normal conditions but high once TGF-β ligands are upregulated under disease conditions. TGF-β1 is a potent growth inhibitor of epidermal keratinocytes, which dictates its tumor suppressive effect in early stages of skin cancer. However, cancer cells lose TGF-β-induced growth inhibition at late stages, and TGF-β-induced angiogenesis and skin inflammation create an environment favorable for skin cancer progression and metastasis. In fibrotic skin diseases, TGF-β plays a key role in activating fibroblast proliferation and stimulating the production of extracellular matrix proteins. Also, TGF-β affects many aspects of skin wound healing and in turn influences cutaneous scarring after skin damage. Fully understanding the mechanisms of TGF-β in the pathogenesis of skin cancer and fibrotic diseases will help design novel strategies in treating skin diseases.

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Acknowledgments

The original work from the Wang laboratory is supported by NIH grants CA79998, CA87849 and AR061792. The authors thank Pamela Garl for carefully proofreading this chapter.

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  1. Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, 80045, USA

    Gangwen Han, Zheyi Han & Xiao-Jing Wang

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    Aristidis Moustakas

  2. , Interdiscip. Grad. Sch. Med. Eng., University of Yamanashi, 1110 Shimokato, Chuo, 409-3898, Yamanashi, Japan

    Keiji Miyazawa

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Han, G., Han, Z., Wang, XJ. (2013). TGF-β in Skin Cancer and Fibrosis. In: Moustakas, A., Miyazawa, K. (eds) TGF-β in Human Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54409-8_9

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