Cells sense and respond to the extracellular matrix (ECM) by way of integrin receptors, which facilitate cell adhesion and intracellular signaling. Advances in understanding the mammary epithelial cell hierarchy are converging with new developments that reveal how integrins regulate the normal mammary gland. But in breast cancer, integrin signaling contributes to the development and progression of tumors. This paper highlights recent studies which examine the role of integrin signaling in mammary epithelial cells and their malignant counterparts. 1. Introduction The extracellular matrix (ECM)—composed of numerous insoluble proteins secreted locally by epithelial and stromal cells—provides physical support to organize neighboring cells within a tissue and serves as a reservoir of growth factors. In the mammary gland, ECM interactions can control epithelial cell proliferation, survival, migration, and differentiation to regulate processes such as branching morphogenesis, polarization of mammary ducts and the alveolar outgrowth, and involution that occurs with pregnancy [1]. However, the matrix, which constitutes one component of the diverse tumor microenvironment, changes dramatically during the process of breast tumorigenesis and can strongly affect disease progression [2]. Therefore, the ECM can exert a strong influence on both normal and tumor cells. In either case, cells sense and respond to the ECM by way of transmembrane integrin receptors, which recognize and bind to various ECM proteins and thereby facilitate cell adhesion and intracellular signaling. Integrins function as a heterodimer, consisting of one α subunit and one β subunit that associate noncovalently. Mammals have 24 distinct integrin receptors, formed from a total of 18 α subunits and 8 β subunits [3]. Integrins couple recognition of ECM ligands to the assembly of the actin cytoskeleton and the activation of various intracellular kinases [4]. Here, we review recent studies that have deepened our understanding of the dynamics and coordination of integrin signaling and of the role that these signals play in mammary epithelial cells and their malignant counterparts. 2. Integrins in Normal Mammary Epithelial Cells With a disease as diverse as breast cancer—in its histology, genetic lesions, proliferation, response to treatment, and propensity to metastasize—it is crucial to examine how the cell type that is initially transformed impacts the tumor that is subsequently formed, a concept which emphasizes the cell of origin for a particular cancer [5]. In this regard, new developments in the
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