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.