Abstract
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.
Highlights
The communication between signaling pathways, the socalled 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
The integrin-cadherin crosstalk is involved in the epithelial-mesenchymal transition (EMT) underlying fundamental physiological and pathological processes, including embryonic development and cancer [22, 25,26,27, 33, 39]
This paper highlights recent growing evidence supporting a major role of reactive oxygen species (ROS) in both outside-in and inside-out signaling of integrins and cadherins, raising the possibility that ROS constitute master regulators of the crosstalk between these fundamental cell adhesion receptors
Summary
The communication between signaling pathways, the socalled 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. There is a large body of evidence supporting the existence of a fine-tuned crosstalk between members of these two adhesive receptor families, which influences their expression, turnover, positioning, and/or functions, and may enhance or suppress adhesion depending on the cellular and environmental context [1, 10, 17, 22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41], the molecules and molecular mechanisms involved in such important phenomenon are not completely defined To clarify how this crosstalk is regulated remains a fundamental challenge for basic and translational research, including research on tumor and vascular disease progression. We discuss the most recent advances on the role of ROS in outside-in and inside-out signal transduction events implicating integrins and cadherins, providing building bloks for the hypothesis that ROS constitute important players in the molecular crosstalk between these cell adhesion receptors
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