Cadherin in Health and Disease

Dear Colleagues,

Mammalian cells dynamically interact with the surrounding microenvironments through cell surface molecules. The main transmembrane component of adherens junctions comprises the family of proteins called cadherins. Classical cadherins mediate a wide range of cellular functions which are important for morphogenesis, tissue homeostasis and physiology, and disease conditions. The diversity of classical cadherins underlies cell recognition specificity and also provides for more specialized tissue-specific functions and signaling events. Cadherins are cell–cell adhesion receptors that act by mediating cell–cell adherence junctions. They interact with a group of linking proteins called catenin, which is essential for cadherin function. Cadherins, which include different types of N-, P-, R-, B-, VE, and E-cadherins, are not only essential for tissue formation but also play a key role in signaling cascade regulation. They are single membrane spanning proteins with a divergent extracellular domain of five repeats and a conserved cytoplasmic domain. Trans interactions are thought to mediate functional interactions between two adjacent cells, while cis interactions are thought to play a key role in stabilizing the adhesion of cell–cell junctions. Binding between cadherin extracellular domains is weak, but strong cell–cell adhesion develops during lateral clustering of cadherins by proteins that link the cadherin cytoplasmic domain to the actin cytoskeleton.

Regulatory mechanisms include control of cadherin gene expression and cadherin switching, cadherin membrane trafficking, cytoskeletal remodeling, and the control of the state of the adhesive bond itself. Signaling mechanisms are essential to classical cadherin functions, contributing to both their intrinsic adhesive and force-generating functions as well as communicating the state of the tissue to mediate changes in growth and differentiation.

Data supporting the widely accepted cadherin ectodomain shedding and its functional consequence in normal physiology and in the tumor environment will be presented. Soluble cadherin fragments may retain specific biological activities during cancer cell invasion, angiogenesis and perineural invasion, and soluble cadherin may represent a novel diagnostic/prognostic biomarker.

Dr. Isabelle Vilgrain
Guest Editor

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• structure
• dimer
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• cell signaling
• kinases
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• SH2 containing proteins
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