Tight junctions (TJs) are the most apical components of the cell–cell adhesion machinery in epithelial and endothelial cells and they play essential roles in homeostasis. Recent studies have revealed that aberrant expression of tight junction proteins (TJPs) is frequently observed in various type of cancers. Here we review cancer-associated aberrant expression of TJPs with focus on transmembrane-type TJPs including claudins, junctional adhesion molecule-A (JAM-A), and occludin. Some transmembrane-type TJPs are upregulated at the early neoplastic stage and their expression persists during dedifferentiation. Aberrant expression of TJPs contributes to proliferation, invasion, and dysregulated signaling of cancer cells. In addition to an increase in their expression level, their localization is altered from a TJ-restricted pattern to distribution throughout the whole cell membrane, making them suitable as therapeutic targets. Extracellular domains of transmembrane-type TJPs can be approached by target drugs not only from the lumen side (apical side) but also from the extracellular matrix side (basal side), including blood vessels. Aberrantly expressed TJPs are potential useful diagnostic markers as well as therapeutic targets for cancers.

中文翻译：

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跨膜型紧密连接蛋白在癌症中的新作用

紧密连接（TJ）是上皮细胞和内皮细胞中细胞-细胞粘附机制的最顶端组成部分，它们在体内平衡中发挥着重要作用。最近的研究表明，紧密连接蛋白（TJP）的异常表达经常在各种类型的癌症中观察到。在这里，我们回顾了与癌症相关的 TJP 异常表达，重点关注跨膜型 TJP，包括密蛋白、连接粘附分子-A (JAM-A) 和 occludin。一些跨膜型 TJP 在肿瘤早期表达上调，并且在去分化过程中持续表达。TJP 的异常表达会导致癌细胞的增殖、侵袭和信号传导失调。除了表达水平增加之外，它们的定位也从 TJ 限制模式改变为分布在整个细胞膜上，使它们适合作为治疗靶点。跨膜型 TJP 的细胞外结构域不仅可以从管腔侧（顶端侧）进入，还可以从包括血管在内的细胞外基质侧（基底侧）进入。异常表达的 TJP 是潜在有用的诊断标记物以及癌症的治疗靶点。