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Roles of Integrins in the Development and Progression of Squamous Cell Carcinomas

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Signaling Pathways in Squamous Cancer

Abstract

The identification of therapeutic targets for inhibiting malignant ­progression and metastasis remains a critically important step in combating cancer mortality in the clinic. Integrins, the major cell surface receptors for cell adhesion to the extracellular matrix, are involved in all stages of carcinogenesis and are promising targets for anti-cancer therapies. Indeed, roles for integrins in cancer have been the focus of intense investigation since this family of cell adhesion receptors was first discovered in the early 1980s, and many studies during the past three decades have described critical functions for integrins expressed on carcinoma cells in controlling proliferation, survival, migration, and angiogenesis. In addition to mediating cell adhesion, integrins serve as conduits of signal transduction across the plasma membrane, thereby mediating information flow between the interior of the tumor cell and the extracellular microenvironment that promotes angiogenesis and drives malignant growth and metastasis. Although a number of integrin antagonists are currently in pre-clinical and clinical development, the repertoire of integrins that is expressed by tumor cells varies considerably among different types of cancer. Therefore, the most effective combination of integrins to target will vary among cancer types and must be determined in each case. In this chapter, we will provide an overview of current knowledge regarding­ tumor-promoting functions of integrins that are expressed in squamous cell ­carcinoma (SCC), and we will consider the prospect of exploiting these integrins as therapeutic­ targets for inhibiting SCC in the clinic.

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Acknowledgments

The authors are grateful to the members of the DiPersio laboratory, and ­colleagues at Albany Medical College, for valuable discussions and insights. Studies conducted by the authors were supported by grants from the NIH/NCI to C.M. DiPersio (R01CA84238, R01CA129637). In addition, J. Lamar was supported by a predoctoral training grant from the National Heart, Lung, and Blood Institute (NIH-T32-HL-07194) and a predoctoral fellowship from the National Cancer Center (06118). We offer our apologies to the many researchers whose valuable contributions to the field could not be cited due to space constraints.

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  1. Center for Cell Biology & Cancer Research, Albany Medical College, 47 New Scotland Avenue, MC 165, Albany, NY, 12208, USA

    C. Michael DiPersio

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  1. John Lamar
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  2. C. Michael DiPersio
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Correspondence to C. Michael DiPersio .

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  1. Center for Molecular Toxicology &, Carcinogenesis, Pennsylvania State University, University Park, 16801, Pennsylvania, USA

    Adam B. Glick

  2. National Institute on Deafness &, Other Communication Disorders, National Institute of Health, Bethesda, 20892, Maryland, USA

    Carter Van Waes

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Lamar, J., DiPersio, C.M. (2011). Roles of Integrins in the Development and Progression of Squamous Cell Carcinomas. In: Glick, A., Waes, C. (eds) Signaling Pathways in Squamous Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7203-3_2

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