Department of Pathology, Sapporo Medical University, Sapporo, Japan; Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan.
Department of Pathology, Sapporo Medical University, Sapporo, Japan.
Biochim Biophys Acta Biomembr. 2021 Mar 1;1863(3):183503. doi: 10.1016/j.bbamem.2020.183503. Epub 2020 Nov 13.
The epithelial-mesenchymal transition (EMT) is an essential step in cancer progression. Epithelial cells possess several types of cell-cell junctions, and tight junctions are known to play important roles in maintaining the epithelial program. EMT is characterized by a loss of epithelial markers, including E-cadherin and tight junction proteins. Somewhat surprisingly, the evidence is accumulating that upregulated expression of tight junction proteins plays an important role in the EMT of cancer cells. Tight junctions have distinct tissue-specific and cancer-specific regulatory mechanisms, enabling them to play different roles in EMT. Tight junctions and related signaling pathways are attractive targets for cancer treatments; signal transduction inhibitors and monoclonal antibodies for tight junction proteins may be used to suppress EMT, invasion, and metastasis. Here we review the role of bicellular and tricellular tight junction proteins during EMT. Further investigation of regulatory mechanisms of tight junctions during EMT in cancer cells will inform the development of biomarkers for predicting prognosis as well as novel therapies.
上皮-间充质转化（EMT）是癌症进展的一个重要步骤。上皮细胞具有多种细胞-细胞连接，而紧密连接被认为在维持上皮程序中发挥重要作用。EMT 的特征是上皮标志物的丧失，包括 E-钙粘蛋白和紧密连接蛋白。令人惊讶的是，越来越多的证据表明，紧密连接蛋白的上调表达在癌细胞的 EMT 中起着重要作用。紧密连接具有独特的组织特异性和癌症特异性调节机制，使它们能够在 EMT 中发挥不同的作用。紧密连接和相关的信号通路是癌症治疗的有吸引力的靶点；紧密连接蛋白的信号转导抑制剂和单克隆抗体可用于抑制 EMT、侵袭和转移。在这里，我们回顾了双细胞和三细胞紧密连接蛋白在 EMT 中的作用。进一步研究 EMT 过程中癌细胞中紧密连接的调节机制将为预测预后的生物标志物的开发以及新疗法的开发提供信息。
