Integrin control of tumor invasion

Abstract

Metastasis is the leading cause of death in cancer patients, and strategies to inhibit tumor cell invasion are a major focus of current efforts to develop cancer treatments. The extracellular matrix (ECM) provides both structural support and extracellular cues that regulate invasive tumor growth, and tumor-associated changes in ECM contribute to cancer progression. Integrins, the major receptors for cell adhesion to ECM, are important at every stage of cancer and occupy a critical position as transducers of chemical and mechanical signals that control tumor cell responses to ECM (i.e., outside-in signaling), as well as tumor-mediated changes to ECM that facilitate invasive growth and metastasis (i.e., inside-out signaling). Integrins are therefore attractive therapeutic targets for antagonistic agents. Here, we provide an overview of cancer-promoting functions of integrins on tumor cells, with a focus on roles in regulating cell invasion, ECM remodeling, tumor angiogenesis, and gene expression. We will also discuss how integrin functions are modulated by ECM ligands outside the cell, cytoskeletal/signaling proteins inside the cell, and other cell surface proteins. Finally, we will discuss current progress towards developing integrin antagonists for clinical use, including barriers that must still be overcome before integrins can be fully exploited as therapeutic targets.