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上皮-间质转化:在癌症进展中的作用及抗肿瘤治疗前景

Epithelial-Mesenchymal Transition: Role in Cancer Progression and the Perspectives of Antitumor Treatment.

作者信息

Gaponova A V, Rodin S, Mazina A A, Volchkov P V

机构信息

Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701 Russia.

Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177 Sweden.

出版信息

Acta Naturae. 2020 Jul-Sep;12(3):4-23. doi: 10.32607/actanaturae.11010.

Abstract

About 90% of all malignant tumors are of epithelial nature. The epithelial tissue is characterized by a close interconnection between cells through cell-cell interactions, as well as a tight connection with the basement membrane, which is responsible for cell polarity. These interactions strictly determine the location of epithelial cells within the body and are seemingly in conflict with the metastatic potential that many cancers possess (the main criteria for highly malignant tumors). Tumor dissemination into vital organs is one of the primary causes of death in patients with cancer. Tumor dissemination is based on the so-called epithelial-mesenchymal transition (EMT), a process when epithelial cells are transformed into mesenchymal cells possessing high mobility and migration potential. More and more studies elucidating the role of the EMT in metastasis and other aspects of tumor progression are published each year, thus forming a promising field of cancer research. In this review, we examine the most recent data on the intracellular and extracellular molecular mechanisms that activate EMT and the role they play in various aspects of tumor progression, such as metastasis, apoptotic resistance, and immune evasion, aspects that have usually been attributed exclusively to cancer stem cells (CSCs). In conclusion, we provide a detailed review of the approved and promising drugs for cancer therapy that target the components of the EMT signaling pathways.

摘要

大约90%的恶性肿瘤具有上皮性质。上皮组织的特点是细胞通过细胞间相互作用紧密相连,并且与负责细胞极性的基底膜紧密连接。这些相互作用严格决定了上皮细胞在体内的位置,似乎与许多癌症所具有的转移潜能(高度恶性肿瘤的主要标准)相冲突。肿瘤扩散到重要器官是癌症患者死亡的主要原因之一。肿瘤扩散基于所谓的上皮-间质转化(EMT),即上皮细胞转化为具有高迁移率和迁移潜能的间质细胞的过程。每年都有越来越多阐明EMT在转移及肿瘤进展其他方面作用的研究发表,从而形成了一个有前景的癌症研究领域。在本综述中,我们研究了激活EMT的细胞内和细胞外分子机制的最新数据,以及它们在肿瘤进展的各个方面(如转移、凋亡抗性和免疫逃逸,这些方面通常仅归因于癌症干细胞(CSCs))所起的作用。总之,我们详细综述了针对EMT信号通路成分的已批准和有前景的癌症治疗药物。

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