Vimentin on the move: new developments in cell migration

Abstract

The vimentin gene ( VIM) encodes one of the 71 human intermediate filament (IF) proteins, which are the building blocks of highly ordered, dynamic, and cell type-specific fiber networks. Vimentin is a multi-functional 466 amino acid protein with a high degree of evolutionary conservation among vertebrates. Vim −/− mice, though viable, exhibit systemic defects related to development and wound repair, which may have implications for understanding human disease pathogenesis. Vimentin IFs are required for the plasticity of mesenchymal cells under normal physiological conditions and for the migration of cancer cells that have undergone epithelial–mesenchymal transition. Although it was observed years ago that vimentin promotes cell migration, the molecular mechanisms were not completely understood. Recent advances in microscopic techniques, combined with computational image analysis, have helped illuminate vimentin dynamics and function in migrating cells on a precise scale. This review includes a brief historical account of early studies that unveiled vimentin as a unique component of the cell cytoskeleton followed by an overview of the physiological vimentin functions documented in studies on Vim −/− mice. The primary focus of the discussion is on novel mechanisms related to how vimentin coordinates cell migration. The current hypothesis is that vimentin promotes cell migration by integrating mechanical input from the environment and modulating the dynamics of microtubules and the actomyosin network. These new findings undoubtedly will open up multiple avenues to study the broader function of vimentin and other IF proteins in cell biology and will lead to critical insights into the relevance of different vimentin levels for the invasive behaviors of metastatic cancer cells.

Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

“…The vimentin IF network has been recently shown to closely associate with other cytoskeletal components to provide a load-bearing "meshwork" supporting the contractile actomyosin system [7].…”

“…Individual cell types express unique IF signatures of more than five different IF proteins, including at least two cytoplasmic IFs and two to three nuclear lamins. In recent decades many IF proteins have been implicated in the regulation of 2D and 3D cell migration [4][5][6], however, to date, only vimentin (Type III) is widely accepted as a major migration enhancer [7].…”

Modulation of cell adhesion and migration by poly-dispersed-acid-functionalized-single-walled carbon nanotubes in lung epithelial cells

“…In addition to increasing cell motility, it also induces physical changes in cell shape, loss of cell-cell contacts, and increased turnover of focal adhesions, factors conducive for migration and metastasis of cancer cells. Integration of mechanical input from the environment and the dynamics of microtubules and the actomyosin network play crucial role in vimentin promoted cell migration process (Mendez et al 2010, Rogel et al 2011,Battaglia 2018.In AF-SWCNTs exposed LA4 and A549 cells, we found no significant changes in the expression of E Cadherin and Claudin -1 with respect to the control that is expected when cell migration is inhibited. E-cadherin is a key molecule of adherens junctions that serves as bridges connecting the cytoskeleton of neighbouring cells through direct interaction.…”

Acto-myosin network geometry defines centrosome position

“…The major intermediate filament in fibroblasts, Vimentin, form a dense network around the nucleus [49]. Because of the elasticity and low dynamics of intermediate filaments, they recovered their initial shape after the enucleation step and formed a circular network with which microtubules kept interacting ( Figure S1).…”