Vimentin contributes to epithelial-mesenchymal transition cancer cell mechanics by mediating cytoskeletal organization and focal adhesion maturation
TLDR
It is demonstrated that vimentin serves as a regulator to maintain intracellular mechanical homeostasis by mediating cytoskeleton architecture and the balance of cell force generation in EMT cancer cells.Abstract:
Modulations of cytoskeletal organization and focal adhesion turnover correlate to tumorigenesis and epithelial-mesenchymal transition (EMT), the latter process accompanied by the loss of epithelial markers and the gain of mesenchymal markers (e.g., vimentin). Clinical microarray results demonstrated that increased levels of vimentin mRNA after chemotherapy correlated to a poor prognosis of breast cancer patients. We hypothesized that vimentin mediated the reorganization of cytoskeletons to maintain the mechanical integrity in EMT cancer cells. By using knockdown strategy, the results showed reduced cell proliferation, impaired wound healing, loss of directional migration, and increased large membrane extension in MDA-MB 231 cells. Vimentin depletion also induced reorganization of cytoskeletons and reduced focal adhesions, which resulted in impaired mechanical strength because of reduced cell stiffness and contractile force. In addition, overexpressing vimentin in MCF7 cells increased cell stiffness, elevated cell motility and directional migration, reoriented microtubule polarity, and increased EMT phenotypes due to the increased β1-integrin and the loss of junction protein E-cadherin. The EMT-related transcription factor slug was also mediated by vimentin. The current study demonstrated that vimentin serves as a regulator to maintain intracellular mechanical homeostasis by mediating cytoskeleton architecture and the balance of cell force generation in EMT cancer cells.read more
Citations
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Journal ArticleDOI
Epithelial-Mesenchymal Transition in Cancer: A Historical Overview
TL;DR: Some of the targeted small molecules utilized as antiproliferative agents have revealed to inhibit EMT initiation or maintenance because EMT is regulated through signaling pathways for which these molecules have been designed.
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Single and collective cell migration: the mechanics of adhesions
TL;DR: An overview of recent developments showing the bidirectional relationship between the physical properties of the environment and the cell mechanical responses during single and collective cell migration is given.
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Are cancer cells really softer than normal cells
Charlotte Alibert,Charlotte Alibert,Bruno Goud,Bruno Goud,Jean-Baptiste Manneville,Jean-Baptiste Manneville +5 more
TL;DR: It is argued that cancer cells can indeed be considered as softer than normal cells, and the intracellular elements that could be responsible for the softening of cancer cells are focused on.
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The Regulatory Role of MicroRNAs in Breast Cancer
Hui-Yi Loh,Brendan P. Norman,Kok-Song Lai,Nik Mohd Afizan Nik Abd Rahman,Noorjahan Banu Alitheen,Mohd Azuraidi Osman +5 more
TL;DR: The current state of research into miRNA involved in breast cancer is highlighted, with particular attention to articles published between the years 2000 to 2019, using detailed searches of the databases PubMed, Google Scholar, and Scopus.
Journal ArticleDOI
The Cytoskeleton-A Complex Interacting Meshwork.
Tim Hohmann,Faramarz Dehghani +1 more
TL;DR: The findings about cytoskeletal filament types, including substructures formed by them, such as lamellipodia, stress fibers, and interactions between intermediate filaments, microtubules and actin are summarized.
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