Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis

作者：Saima Usman, Naushin Waseem, Thuan Khanh Ngoc Nguyen, Sahar Mohsin, Ahmad Jamal, Muy‐Teck Teh, Ahmad Waseem · 发表于：Cancers · 年份：2021 · DOI：10.3390/cancers13194985 · 被引用次数：448 · 研究领域：Skin and Cellular Biology Research、Cancer Cells and Metastasis、Wnt/β-catenin signaling in development and cancer

Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. This review highlights the pivotal role of vimentin in the key events during EMT and explains its role as a downstream as well as an upstream regulator in this highly complex process. This review also highlights the areas that require further research in exploring the role of vimentin in EMT. As a cytoskeletal protein, vimentin filaments support mechanical integrity of the migratory machinery, generation of directional force, focal adhesion modulation and extracellular attachment. As a viscoelastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. However, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In...