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

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.

Selection and Characterization of Vimentin-Binding Aptamer Motifs for Ovarian Cancer

“…Although vimentin is mainly found in fibroblast, endothelial cells, macrophages, and lymphocytes, collective evidence suggest that the aberrant expression of vimentin in epithelial cancer cells is related to the epithelial-mesenchymal transition (EMT) and associated with tumor initiation, invasion, metastasis, and resistance to therapy [30,31]. Therefore, we used the ovarian tumor samples to assess the binding of V3M2 and V5M2 to vimentin expression ovarian tumors.…”

“…To quantitatively evaluate the binding affinity of selected V3M2 and V5M2 further, vimentin expressing IGROV cells were incubated with biotin conjugates motifs at various concentrations (31,125, 500 nM for V3M2, and 41, 166, 666 nM for V5M2), followed by streptavidin-FITC staining. The binding affinity of V3M2 and V5M2 at various concentrations was determined by mean fluorescence intensity using flow cytometry.…”

The Effect of Vitamin D3 and Silver Nanoparticles on HaCaT Cell Viability

“…In line with this, our results showed a high amount of the cells positive to cytokeratin and negative to vimentin in control and VD3 + AgNPs treated samples. However, interestingly, we also observed a low cell number negative to cytokeratin and a low cell number positive to vimentin only in VD3 + AgNPs treated samples, indicating a differentiation of some keratinocytes with their epithelial-mesenchymal transition useful for the wound healing [9,10]. As a negative control of immunohistochemical analysis, we used α-smooth muscle actin (α-SMA, Figure 3).…”

“…Interestingly, the combination of 133 nM VD3 and 5 ppm AgNP stimulated complete wound closure only after 18 h. Cellular hypercolourability as evident in the closing line. To investigate the possible molecular mechanisms involved in VD3 + AgNPs wound repair, we analyzed the expression of cytokeratin as an epithelial marker and vimentin as a mesenchymal marker [10] in cells after 24 h from treatment (Figure 3). In line with this, our results showed a high amount of the cells positive to cytokeratin and negative to vimentin in control and VD3 + AgNPs treated samples.…”

“…It is known that wound repair takes place thanks to the proliferation of keratinocytes and their transdifferentiation to mesenchymal cells epithelial-mesenchymal transition (EMT) [9]. Among EMT forms, the type 2 is specific of wound healing [10].…”