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Mechanism and regulation of epithelial–mesenchymal transition in cancer

机译:癌症上皮-间质转化的机制和调控

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Abstract: During development and the pathogenesis of certain diseases, including cancer, the epithelial–mesenchymal transition (EMT) program is activated. It is hypothesized that EMT plays a major role in tumor invasion and the establishment of distant metastases. Metastatic disease is responsible for the vast majority of cancer-related deaths, which provides a precedent for elucidating pathways that regulate EMT. EMT is defined as the transition of cells with an epithelial phenotype into cells with a mesenchymal phenotype through a series of genetic and environmental events. This leads to the repression of epithelial-associated markers, upregulation of mesenchymal-associated markers, a loss of cell polarity and adhesion, and increased cell motility and invasiveness. EMT is a reversible and dynamic process, and can be regulated by signals from the microenvironment such as inflammation, hypoxia, and growth factors or epigenetically via microRNAs. These signals modulate key EMT-associated transcription factors and effector proteins that control cellular phenotype and regulate tumor plasticity in response to changing conditions in the microenvironment and the progressive nature of cancer. Understanding the complex regulatory networks controlling EMT can provide insight into tumor progression and metastasis.
机译:摘要:在某些疾病(包括癌症)的发生和发病机理中,上皮-间质转化(EMT)程序被激活。假设EMT在肿瘤侵袭和远处转移的建立中起主要作用。转移性疾病是绝大多数与癌症相关的死亡的原因,这为阐明调节EMT的途径提供了先例。 EMT被定义为通过一系列遗传和环境事件将具有上皮表型的细胞转变为具有间充质表型的细胞。这导致上皮相关标志物的抑制,间充质相关标志物的上调,细胞极性和粘附性的丧失以及细胞运动性和侵袭性的增加。 EMT是一个可逆的动态过程,可以通过来自微环境的信号(例如炎症,缺氧和生长因子)进行调控,也可以通过表观遗传学通过microRNA进行调控。这些信号可调节关键的EMT相关转录因子和效应蛋白,从而控制细胞表型并调节肿瘤可塑性,以响应微环境中不断变化的状况和癌症的进展特性。了解控制EMT的复杂调控网络可以深入了解肿瘤的进展和转移。

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