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

被引:404
作者
Liu, Ching-Yi [1 ,2 ]
Lin, Hsi-Hui [2 ]
Tang, Ming-Jer [1 ,2 ]
Wang, Yang-Kao [1 ,3 ,4 ]
机构
[1] Natl Cheng Kung Univ, Inst Basic Med Sci, Tainan 70101, Taiwan
[2] Natl Cheng Kung Univ, Dept Physiol, Tainan 70101, Taiwan
[3] Natl Cheng Kung Univ, Dept Cell Biol & Anat, Tainan 70101, Taiwan
[4] Taipei Med Univ, Ctr Neurotrauma & Neuroregenerat, Taipei, Taiwan
关键词
vimentin; epithelial-mesenchymal transition (EMT); microtubule; focal adhesions; cell stiffness; INTERMEDIATE-FILAMENTS; BREAST-CANCER; COLORECTAL-CANCER; ENDOTHELIAL-CELLS; GENE-EXPRESSION; INTEGRIN; MICROTUBULES; MIGRATION; METASTASIS; STIFFNESS;
D O I
10.18632/oncotarget.3862
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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, over expressing vimentin in MCF7 cells increased cell stiffness, elevated cell motility and directional migration, reoriented microtubule polarity, and increased EMT phenotypes due to the increased beta 1-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.
引用
收藏
页码:15966 / 15983
页数:18
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