Adhesion

Cadherins are a superfamily of transmembrane glycoproteins that contain cadherin repeats of approximately 100 residues in their extracellular domain. Cadherins mediate calcium-dependent cell-cell adhesion and play critical roles in normal tissue development (1). The classic cadherin subfamily includes N-, P-, R-, B- and E-cadherins as well as about ten other members that are found in adherens junctions, a cellular structure near the apical surface of polarized epithelial cells. The cytoplasmic domain of classical cadherins interacts with β-catenin, γ-catenin (also called plakoglobin), and p120 catenin. β-catenin and γ-catenin associate with α-catenin, which links the cadherin-catenin complex to the actin cytoskeleton (1,2). While β- and γ-catenin play structural roles in the junctional complex, p120 regulates cadherin adhesive activity and trafficking (1-4). E-cadherin is considered an active suppressor of invasion and growth of many epithelial cancers (1-3). Recent studies indicate that cancer cells have up-regulated N-cadherin in addition to loss of E-cadherin. This change in cadherin expression is called the "cadherin switch". N-cadherin cooperates with the FGF receptor, leading to overexpression of MMP-9 and cellular invasion (3). In endothelial cells, VE-cadherin signaling, expression, and localization correlate with vascular permeability and tumor angiogenesis (5,6). Expression of P-cadherin, which is normally present in epithelial cells, is also altered in ovarian and other human cancers (7,8).

1. Wheelock, M.J. and Johnson, K.R. (2003) Annu. Rev. Cell. Dev. Biol. 19, 207-235.
2. Christofori, G. (2003) EMBO J. 22, 2318-2323.
3. Hazan, R.B. et al. (2004) Ann. NY Acad. Sci. 1014, 155-163.
4. Bryant, D.M. and Stow, J.L. (2004) Trends Cell Biol. 14, 427-434.
5. Rabascio, C. et al. (2004) Cancer Res. 64, 4373-4377.
6. Yamaoka-Tojo, M. et al. (2006) Arterioscler. Thromb. Vasc. Biol. 26, 1991-1997.
7. Patel, I.S. et al. (2003) Int. J. Cancer 106, 172-177.
8. Sanders, D.S. et al. (2000) J. Pathol. 190, 526-530.

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E-Cadherin Blocking Peptide

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