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癌症进展过程中 EMT 和 TGF-β 信号转导中的可变剪接。

Alternative splicing in EMT and TGF-β signaling during cancer progression.

机构信息

Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

出版信息

Semin Cancer Biol. 2024 Jun;101:1-11. doi: 10.1016/j.semcancer.2024.04.001. Epub 2024 Apr 15.

Abstract

Epithelial to mesenchymal transition (EMT) is a physiological process during development where epithelial cells transform to acquire mesenchymal characteristics, which allows them to migrate and colonize secondary tissues. Many cellular signaling pathways and master transcriptional factors exert a myriad of controls to fine tune this vital process to meet various developmental and physiological needs. Adding to the complexity of this network are post-transcriptional and post-translational regulations. Among them, alternative splicing has been shown to play important roles to drive EMT-associated phenotypic changes, including actin cytoskeleton remodeling, cell-cell junction changes, cell motility and invasiveness. In advanced cancers, transforming growth factor-β (TGF-β) is a major inducer of EMT and is associated with tumor cell metastasis, cancer stem cell self-renewal, and drug resistance. This review aims to provide an overview of recent discoveries regarding alternative splicing events and the involvement of splicing factors in the EMT and TGF-β signaling. It will emphasize the importance of various splicing factors involved in EMT and explore their regulatory mechanisms.

摘要

上皮-间充质转化 (EMT) 是发育过程中的一种生理过程,在此过程中上皮细胞转变为获得间充质特征,从而允许它们迁移并定植于次级组织。许多细胞信号通路和主转录因子发挥着无数的控制作用,以微调这一重要过程,以满足各种发育和生理需求。使这个网络变得更加复杂的是转录后和翻译后调控。其中,选择性剪接已被证明在驱动 EMT 相关表型变化中发挥重要作用,包括肌动蛋白细胞骨架重塑、细胞-细胞连接变化、细胞迁移和侵袭。在晚期癌症中,转化生长因子-β (TGF-β) 是 EMT 的主要诱导因子,与肿瘤细胞转移、癌症干细胞自我更新和耐药性有关。本综述旨在概述关于选择性剪接事件的最新发现,以及剪接因子在 EMT 和 TGF-β 信号中的参与。它将强调 EMT 中涉及的各种剪接因子的重要性,并探讨它们的调节机制。

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