The coordinate modulation of the cellular functions of cadherins and integrins plays an essential role in fundamental physiological and pathological processes, including morphogenesis, tissue differentiation and renewal, wound healing, immune surveillance, inflammatory response, tumor progression, and metastasis. However, the molecular mechanisms underlying the fine-tuned functional communication between cadherins and integrins are still elusive. This paper focuses on recent findings towards the involvement of reactive oxygen species (ROS) in the regulation of cell adhesion and signal transduction functions of integrins and cadherins, pointing to ROS as emerging strong candidates for modulating the molecular crosstalk between cell-matrix and cell-cell adhesion receptors. 1. Introduction The communication between signaling pathways, the so-called molecular crosstalk, plays a central role in cell biology, enabling the cell to couple the molecular functions of either near neighbors or distant cell components, with resulting synergistic or antagonistic effects and eventually appropriate biological outcomes. Among the most important cellular crosstalk events is the signaling network that couples the molecular functions of adhesion receptors of the integrin and cadherin families. Indeed, acting in concert with growth factor receptor signaling pathways, this regulatory network is fundamentally important during the entire life of all metazoans, whereas its dysfunction almost invariably leads to developmental defects and/or diseases, including genetic diseases and cancer [1]. Integrins and cadherins are the major cell-extracellular matrix (ECM) and cell-cell adhesion receptors, respectively, and represent critical determinants of tissue architecture and function both in developing and adult organisms [2, 3]. Integrins are heterodimeric transmembrane glycoproteins composed of noncovalently linked α and β subunits, which are endowed with both structural and regulatory functions. They link the ECM to several distinct cytoplasmic proteins and the actin cytoskeleton at focal adhesions, thus serving as organizing centers for the assembly of structural and regulatory protein complexes at discrete cell-matrix adhesion sites and providing a mechanically sensitive system for mechanotransduction [4]. Furthermore, often acting in concert with growth factor receptors, they provide both outside-in and inside-out transmission of signals across the plasma membrane that control a number of critical cellular processes, including adhesion, cytoskeleton remodeling, migration,
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