CD82 and Cell-Cell Adhesion in Metastatic Prostate Cancer.

摘要

CD82 is a non enzymatic transmembrane molecular scaffold that was initially identified as a metastasis suppressor in the rat AT6.1 prostate tumor model (1). CD82 has been shown to regulate several key factors important for metastasis, including growth factor receptor signaling, (Epidermal Growth Factor Receptor and Hepatocyte Growth Factor Receptor) and Ecadherin (2 6). E cadherin is responsible for the formation of adherens junctions in the cell, a multi molecular complex that regulates epithelial cell polarity and cell cell adhesion. Loss of cell cell adhesion and apical basal cellular polarity are hallmarks of metastatic cancer, loss of which are required for escape from the primary tumor and extravasation into the blood stream. Tetraspanin family members including CD82 form membrane microdomains on the cell surface, known as Tetraspanin Enriched Microdomains (TEMs) that serve to regulate interacting partners by their inclusion or exclusion from these domains (7). These domains are light in density, and float in the light density fractions upon cellular density gradient fractionation, allowing biochemical analysis of proteins localizing in TEMS. Although CD82 regulates multiple signaling molecules, the mechanisms by which it does so remain poorly defined. The purpose of this study was to determine whether there are any structural determinants within CD82 that define its ability to regulate E cadherin in TEMs. While CD82 has a known Y X X internalization motif (8), no other interaction domains within the protein have been identified.