Mandicourt Guillaume, Iden Sandra, Ebnet Klaus, Aurrand-Lions Michel, Imhof Beat A
Department of Pathology and Immunology, the University Medical Center, CH 1211 Geneva 4, Switzerland.
J Biol Chem. 2007 Jan 19;282(3):1830-7. doi: 10.1074/jbc.M605666200. Epub 2006 Nov 12.
Junctional Adhesion Molecules (JAMs) have been described as major components of tight junctions in endothelial and epithelial cells. Tight junctions are crucial for the establishment and maintenance of cell polarity. During tumor development, they are remodeled, enabling neoplastic cells to escape from constraints imposed by intercellular junctions and to adopt a migratory behavior. Using a carcinoma cell line we tested whether JAM-C could affect tight junctions and migratory properties of tumor cells. We show that transfection of JAM-C improves the tight junctional barrier in tumor cells devoid of JAM-C expression. This is dependent on serine 281 in the cytoplasmic tail of JAM-C because serine mutation into alanine abolishes the specific localization of JAM-C in tight junctions and establishment of cell polarity. More importantly, the same mutation stimulates integrin-mediated cell migration and adhesion via the modulation of beta1 and beta3 integrin activation. These results highlight an unexpected function for JAM-C in controlling epithelial cell conversion from a static, polarized state to a pro-migratory phenotype.
连接粘附分子（JAMs）被认为是内皮细胞和上皮细胞紧密连接的主要组成部分。紧密连接对于细胞极性的建立和维持至关重要。在肿瘤发生过程中，紧密连接会发生重塑，使肿瘤细胞能够摆脱细胞间连接所施加的限制，并表现出迁移行为。我们使用一种癌细胞系来测试JAM-C是否会影响肿瘤细胞的紧密连接和迁移特性。我们发现，转染JAM-C可改善缺乏JAM-C表达的肿瘤细胞的紧密连接屏障。这依赖于JAM-C细胞质尾巴中的丝氨酸281，因为将丝氨酸突变为丙氨酸会消除JAM-C在紧密连接中的特异性定位以及细胞极性的建立。更重要的是，相同的突变通过调节β1和β3整合素的激活来刺激整合素介导的细胞迁移和粘附。这些结果突出了JAM-C在控制上皮细胞从静态、极化状态转变为促迁移表型方面的意外功能。
