The role of Vimentin in Regulating Cell Invasive Migration in Dense Cultures of Breast Carcinoma Cells

Abstract

Cell migration and mechanics are tightly regulated by the integrated activities of the various cytoskeletal networks. In cancer cells, cytoskeletal modulations have been implicated in the loss of tissue integrity and acquisition of an invasive phenotype. In epithelial cancers, for example, increased expression of the cytoskeletal filament protein vimentin correlates with metastatic potential. Nonetheless, the exact mechanism whereby vimentin affects cell motility remains poorly understood. In this study, we measured the effects of vimentin expression on the mechano-elastic and migratory properties of the highly invasive breast carcinoma cell line MDA231. We demonstrate here that vimentin stiffens cells and enhances cell migration in dense cultures, but exerts little or no effect on the migration of sparsely plated cells. These results suggest that cell-cell interactions play a key role in regulating cell migration, and coordinating cell movement in dense cultures. Our findings pave the way toward understanding the relationship between cell migration and mechanics in a biologically relevant context.

Hypermethylated in cancer 1 (HIC1) suppresses bladder cancer progression by targeting yes‐associated protein (YAP) pathway

“…Figure 2F showed a decrease in YAP upon HIC1 overexpression and an increase in it upon HIC1 knockdown. 35 The expression of E-cadherin and ZO-1 was found significantly increased in the HIC1-overexpressed group but decreased in the HIC1knockdown group; the opposite was found for the expression of N-cadherin and vimentin ( Figure 3C). The migratory and invasive ability was examined by the means of wound healing ( Figure 3A) and transwell migration assay ( Figure 3B), respectively.…”

Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

“…Simultaneously, vimentin itself has a role in modulating EMT signaling. Vimentin levels seem to regulate Snail expression in a feedback loop, and a knock-down of vimentin resulted in decreased Snail1 mRNA levels [12]. Over-expression of vimentin leads to an increase in Slug expression levels, while down-regulation has the opposite effect [10].…”

“…Over-expression of vimentin in epithelial cells has been shown to be sufficient for cells to adopt the elongated shape typical of mesenchymal cells. This is followed by the reorganization of the actin and microtubule cytoskeletons [10], the internalization of desmosomes [11], and the rearrangement of keratin IFs [12]. Conversely, downregulation of vimentin not only hampers the migration of a large variety of tumor cell lines [4] but also partially restores their epithelial phenotype [13].EMT is governed by several signaling pathways that exhibit complex interactions with vimentin, as demonstrated in numerous studies.…”

“…It has been reported that Twist1 activates the expression of Cullin2 circular RNA (circ-10720), which absorbs miRNA targeting vimentin, leading to increased vimentin mRNA levels [29].Simultaneously, vimentin itself has a role in modulating EMT signaling. Vimentin levels seem to regulate Snail expression in a feedback loop, and a knock-down of vimentin resulted in decreased Snail1 mRNA levels [12]. Over-expression of vimentin leads to an increase in Slug expression levels, while down-regulation has the opposite effect [10].…”

Lateral Subunit Coupling Determines Intermediate Filament Mechanics

“…It has been shown that vimentin deprived cells are less mechanically stable and migrate more slowly [5], whereas cells lacking keratin are softer and more deformable [6,7]. These differences are likely to play an important role during endothelial-tomesenchymal transition (EMT), for example in embryogenesis, wound healing and cancer metastasis, when cells upregulate vimentin expression and downregulate keratin expression [4,[8][9][10]. We hypothesize that keratin and vimentin IFs have different mechanical properties already at the single filament level.…”