Department of Surgery, Vanderbilt University Medical Center, Nashville, TN37232, USA.
J Oncol. 2010;2010:541957. doi: 10.1155/2010/541957. Epub 2010 Jul 8.
Tight junctions are the apical cell-cell adhesion that regulate paracellular permeability and are critical for epithelial cell polarity. Molecular architecture of tight junction has been studied extensively, which has confirmed that claudin family of proteins is integral component of tight junction. Loss of cell-cell adhesion is central to the cellular transformation and acquisition of metastatic potential; however, the role of claudin family of proteins play in a series of pathophysiological events, including human carcinoma development, is only now beginning to be understood. Several claudin mouse knockout models have been generated and the diversity of phenotypes observed clearly demonstrates their important roles in the maintenance of tissue integrity in various organs and suggest that claudins also participate in cellular contexts other than tight junctions. The mechanisms of claudin regulation and their exact roles in normal physiology and disease are being elucidated, but much work remains to be done. In this review, we have discussed the conceptual framework concerning claudins and their potential implication in cancer. We predict that next several years will likely witness a boom in our understanding of the potential role of claudins in the regulation of tumorigenesis, which may, in turn, provide new approaches for the targeted therapy.
紧密连接是位于顶端的细胞-细胞黏附连接,调节细胞旁通透性,对于上皮细胞极性至关重要。紧密连接的分子结构已被广泛研究,证实了紧密连接蛋白家族是紧密连接的组成部分。细胞-细胞黏附的丧失是细胞转化和获得转移潜能的核心;然而,紧密连接蛋白家族在一系列病理生理事件中的作用,包括人类癌的发生,目前才刚刚开始被理解。已经产生了几种紧密连接蛋白敲除的小鼠模型,观察到的表型多样性清楚地表明它们在维持各种器官组织完整性中的重要作用,并表明紧密连接蛋白也参与了除紧密连接以外的细胞环境。紧密连接蛋白的调节机制及其在正常生理和疾病中的确切作用正在阐明,但仍有许多工作要做。在这篇综述中,我们讨论了关于紧密连接蛋白的概念框架及其在癌症中的潜在意义。我们预测,未来几年可能会见证我们对紧密连接蛋白在肿瘤发生调节中的潜在作用的理解的蓬勃发展,这反过来可能为靶向治疗提供新的方法。