Gloushankova N A, Zhitnyak I Y, Rubtsova S N
Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115478, Russia.
Biochemistry (Mosc). 2018 Dec;83(12):1469-1476. doi: 10.1134/S0006297918120052.
Epithelial-mesenchymal transition (EMT) is a fundamental process of morphogenesis whereby epithelial cells acquire the mesenchymal phenotype. Multiple data suggest a critical role of EMT in tumor progression. In carcinomas, EMT can be initiated and promoted by many oncogenic signaling pathways, hypoxia, and signals of tumor microenvironment resulting in epithelial cells losing their cell polarity and cell-cell adhesion and gaining the migratory and invasive properties. Downregulation of expression of the cell adhesion protein E-cadherin is considered a poor prognostic factor in cancer. Many tumors are characterized by incomplete EMT, where tumor cells acquire mesenchymal characteristics but retain their epithelial markers, in particular, E-cadherin. In cells with the hybrid epithelial-mesenchymal phenotype, E-cadherin is accumulated in adherens junctions which are less stable than adherens junctions in normal epithelial cells. E-cadherin-based adherens junctions are essential for efficient collective migration and invasion of carcinoma cells, and their survival in metastasis. The plasticity of the hybrid epithelial-mesenchymal phenotype improves adaptive capabilities of cancer cells. By undergoing EMT, carcinoma cells become resistant to chemotherapy and acquire the ability to suppress immune response. Emergence of cancer stem cells after EMT activation has been observed in many types of carcinoma.
上皮-间质转化（EMT）是一种基本的形态发生过程，通过该过程上皮细胞获得间质表型。多项数据表明EMT在肿瘤进展中起关键作用。在癌中，EMT可由多种致癌信号通路、缺氧及肿瘤微环境信号引发和促进，导致上皮细胞丧失细胞极性和细胞间黏附，获得迁移和侵袭特性。细胞黏附蛋白E-钙黏蛋白表达下调被认为是癌症预后不良的因素。许多肿瘤的特征是不完全EMT，即肿瘤细胞获得间质特征但保留其上皮标志物，尤其是E-钙黏蛋白。在具有混合上皮-间质表型的细胞中，E-钙黏蛋白积聚在黏着连接处，这些黏着连接比正常上皮细胞中的黏着连接更不稳定。基于E-钙黏蛋白的黏着连接对于癌细胞有效的集体迁移和侵袭及其在转移中的存活至关重要。混合上皮-间质表型的可塑性提高了癌细胞的适应能力。通过经历EMT，癌细胞对化疗产生抗性并获得抑制免疫反应的能力。在许多类型的癌中已观察到EMT激活后癌症干细胞的出现。
