Vimentin is at the heart of epithelial mesenchymal transition (Emt) mediated metastasis

Saima Usman, Naushin H. Waseem, Thuan Khanh Ngoc Nguyen, Sahar Mohsin, Ahmad Jamal, Muy Teck Teh, Ahmad Waseem

Research output: Contribution to journalReview articlepeer-review

31 Citations (Scopus)

Abstract

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 angiogen-esis. 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 visco-elastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. How-ever, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In addition, it suppresses cellular differentiation and upregulates their pluripotent potential by inducing genes associated with self-renewability, thus increasing the stemness of cancer stem cells, facilitating the tumour spread and making them more resistant to treatments. Several missense and frameshift mutations reported in vimentin in human cancers may also contribute towards the metastatic spread. Therefore, we propose that vimentin should be a therapeutic target using molecular technologies that will curb cancer growth and spread with re-duced mortality and morbidity.

Original languageEnglish
Article number4985
JournalCancers
Volume13
Issue number19
DOIs
Publication statusPublished - Oct 1 2021

Keywords

  • Amoeboid movement
  • Cancer invasion
  • Cancer stem cells
  • Epithelial tu-mours
  • Mesenchymal epithelial transition

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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