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Integrins and Cancer

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The Tumor Microenvironment

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Integrins are heterodimeric transmembrane glycoproteins that bind extracellular matrix (ECM) proteins and thereby functionally couple the cytoskeleton to the extracellular environment. The relationship between integrins and cancer has been widely studied as malignant cells alter not only integrin expression and organization, but properties of the surrounding ECM as well. Although integrin cytoplasmic tails lack direct kinase activity, interaction with multiple adaptor proteins enables the assembly of signaling complexes that result in the activation of focal adhesion kinase (FAK) or integrin-linked kinase (ILK). These phosphorylation events trigger downstream signaling pathways that activate a variety of cellular responses key to tumor progression including survival, proliferation, motility, and invasion. In addition, gene expression changes induced by integrin signaling have been implicated in epithelial-to-mesenchymal transition (EMT), most notably via downregulation of E-cadherin expression and function. Emerging evidence that integrin-mediated ECM adhesion is inherently a mechanosensory process also supports a role for integrin-mediated mechanotransduction in tumor progression and metastasis. Together these studies suggest that integrin-directed therapeutics combined with strategies designed to target the mechanical properties of the ECM and restore normal tissue architecture may provide new options as single agent or combined anticancer therapies.

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Acknowledgments

This work was supported by National Institutes of Health/National Cancer Institutes Research Grants CA109545 (MSS, LGH), CA086984 (MSS), CA085870 (MSS), and GM079381 (LGH).

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  1. Department of Pathology & Anatomical Sciences, Medical Physiology and Pharmacology, University of Missouri School of Medicine, 1 Hospital Drive, M214C Medical Sciences Bldg., Columbia, MO, 65212, USA

    M. Sharon Stack

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  1. Laurie G. Hudson
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  2. M. Sharon Stack
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Correspondence to M. Sharon Stack .

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  1. Genzyme Corporation, Mountain Rd. 1, Framingham, 01701-9322, Massachusetts, USA

    Rebecca G. Bagley

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Hudson, L.G., Stack, M.S. (2010). Integrins and Cancer. In: Bagley, R. (eds) The Tumor Microenvironment. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6615-5_24

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  • DOI: https://doi.org/10.1007/978-1-4419-6615-5_24

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