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

SIMPLE SUMMARY: Vimentin is an important filamentous protein providing structural and functional support to the cell. During initial stages of cancer development, vimentin concentration is very low, however, it increases when cancer starts to invade the surrounding areas. This review highlights the varied roles of vimentin in cancer growth and its spread to distant areas of the body. We have tried to explore the potential new areas of research related to the role of vimentin in cancer progression. We have also highlighted the reported damage to the vimentin gene in cancers, although how the damaged vimentin helps in cancer growth and spread is not known. We propose that latest technologies should be employed to medicinally target vimentin to reduce the cancer growth and its spread thereby helping to increase treatment outcomes and patients’ survival. 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 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 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 reduced mortality and morbidity.