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Metastasising Fibro...
Metastasising Fibroblasts Show an HDAC6-Dependent Increase in Migration Speed and Loss of Directionality Linked to Major Changes in the Vimentin Interactome
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- Evans, Caroline A. (author)
- Univ Sheffield, Dept Chem & Biol Engn, Mappin St, Sheffield S1 3JD, S Yorkshire, England.
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- Kim, Hyejeong Rosemary (author)
- Univ Sheffield, Med Sch, Dept Oncol & Metab, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England.
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- Macfarlane, Sarah C. (author)
- Univ Sheffield, Med Sch, Dept Oncol & Metab, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England.
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- Nowicki, Poppy I. A. (author)
- Univ Sheffield, Med Sch, Dept Oncol & Metab, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England.
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- Baltes, Carsten (author)
- Saarland Univ, NT Fac, Expt Phys, D2 2, D-66123 Saarbrucken, Germany.
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- Xu, Lei (author)
- KTH,Kvant- och biofotonik
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- Widengren, Jerker (author)
- KTH,Kvant- och biofotonik
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- Lautenschlaeger, Franziska (author)
- Saarland Univ, NT Fac, Expt Phys, D2 2, D-66123 Saarbrucken, Germany.
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- Corfe, Bernard M. (author)
- Newcastle Univ, Populat Hlth Sci Inst, Fac Med Sci, Human Nutr Res Ctr, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
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- Gad, Annica K. B. (author)
- Univ Sheffield, Med Sch, Dept Oncol & Metab, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England.;Univ Madeira, Madeira Chem Res Ctr, P-9020105 Funchal, Portugal.
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Univ Sheffield, Dept Chem & Biol Engn, Mappin St, Sheffield S1 3JD, S Yorkshire, England Univ Sheffield, Med Sch, Dept Oncol & Metab, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England. (creator_code:org_t)
- 2022-02-10
- 2022
- English.
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:4
- Related links:
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https://doi.org/10.3...
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Abstract
Subject headings
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- Metastasising cells express the intermediate filament protein vimentin, which is used to diagnose invasive tumours in the clinic. We aimed to clarify how vimentin regulates the motility of metastasising fibroblasts. STED super-resolution microscopy, live-cell imaging and quantitative proteomics revealed that oncogene-expressing and metastasising fibroblasts show a less-elongated cell shape, reduced cell spreading, increased cell migration speed, reduced directionality, and stronger coupling between these migration parameters compared to normal control cells. In total, we identified and compared 555 proteins in the vimentin interactome. In metastasising cells, the levels of keratin 18 and Rab5C were increased, while those of actin and collagen were decreased. Inhibition of HDAC6 reversed the shape, spreading and migration phenotypes of metastasising cells back to normal. Inhibition of HDAC6 also decreased the levels of talin 1, tropomyosin, Rab GDI beta, collagen and emilin 1 in the vimentin interactome, and partially reversed the nanoscale vimentin organisation in oncogene-expressing cells. These findings describe the changes in the vimentin interactome and nanoscale distribution that accompany the defective cell shape, spreading and migration of metastasising cells. These results support the hypothesis that oncogenes can act through HDAC6 to regulate the vimentin binding of the cytoskeletal and cell-extracellular matrix adhesion components that contribute to the defective motility of metastasising cells.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- oncogenes
- metastasis
- cell migration
- histone deacetylase 6
- vimentin
- vimentin interactome
- fibroblasts
- genome-wide mass spectrometry
- stimulated emission depletion microscopy
Publication and Content Type
- ref (subject category)
- art (subject category)
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Evans, Caroline ...
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Kim, Hyejeong Ro ...
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Macfarlane, Sara ...
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Nowicki, Poppy I ...
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Baltes, Carsten
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Xu, Lei
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Widengren, Jerke ...
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Lautenschlaeger, ...
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Corfe, Bernard M ...
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Gad, Annica K. B ...
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- MEDICAL AND HEALTH SCIENCES
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Royal Institute of Technology