Cadherins are a multifunctional family of Ca2+-dependent, transmembrane glycoproteins which promote and maintain cell adhesion in virtually all multicellular organisms. The cadherin superfamily comprises over forty proteins which are, on average, 50-60% homologous. Cadherin expression is required for the assembly of cells into solid tissues and importantly, cadherins are expressed in a tissue specific fashion. Homotypic cellular interactions are promoted by homophillic interactions between the extracellular regions of like cadherin molecules on neighboring cells. Recent crystal structure analysis of an extracellular cadherin domain suggests that individual cadherin molecules cooperate to form a linear cell adhesion zipper. In adherens junctions, cadherins are anchored to the actin cytoskeleton by interaction with the small cytoplasmic proteins b-catenin and γ-catenin which both bind to the actin binding protein a-catenin.bThe interaction of b- catenin with the cytoplasmic tail of cadherins and other cytoplasmic proteins, including Tcf-family transcription factors and the tumor suppressor protein APC, is thought to be mediated through a region of the b-catenin molecule containing multiple repeats of the 42 amino acid armadillo sequence motif. In addition to playing important roles in differentiation and tissue morphogenesis, cadherins also appear to play a significant role in modulating tumor invasion and metastasis. The expression of E-cadherin correlates inversely with the motile and invasive behavior of tumor cells.
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