Vimentin contributes to epithelial-mesenchymal transition ancer cell mechanics by mediating cytoskeletal organization and focal adhesion maturation

Ching Yi Liu, Hsi Hui Lin, Ming Jer Tang, Yang Kao Wang

    Research output: Contribution to journalArticle

    119 Citations (Scopus)

    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 ß1-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.

    Original languageEnglish
    Pages (from-to)15966-15983
    Number of pages18
    JournalOncotarget
    Volume6
    Issue number18
    Publication statusPublished - 2015

    Fingerprint

    Focal Adhesions
    Epithelial-Mesenchymal Transition
    Vimentin
    Mechanics
    Cytoskeleton
    MCF-7 Cells
    Cadherins
    Integrins
    Microtubules
    Wound Healing
    Cell Movement
    Neoplasms
    Carcinogenesis
    Homeostasis
    Cell Proliferation
    Breast Neoplasms
    Phenotype
    Drug Therapy
    Messenger RNA
    Membranes

    Keywords

    • Cell stiffness
    • Epithelial-mesenchymal transition (EMT)
    • Focal adhesions
    • Microtubule
    • Vimentin

    ASJC Scopus subject areas

    • Oncology

    Cite this

    Vimentin contributes to epithelial-mesenchymal transition ancer cell mechanics by mediating cytoskeletal organization and focal adhesion maturation. / Liu, Ching Yi; Lin, Hsi Hui; Tang, Ming Jer; Wang, Yang Kao.

    In: Oncotarget, Vol. 6, No. 18, 2015, p. 15966-15983.

    Research output: Contribution to journalArticle

    Liu, Ching Yi ; Lin, Hsi Hui ; Tang, Ming Jer ; Wang, Yang Kao. / Vimentin contributes to epithelial-mesenchymal transition ancer cell mechanics by mediating cytoskeletal organization and focal adhesion maturation. In: Oncotarget. 2015 ; Vol. 6, No. 18. pp. 15966-15983.
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