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Vimentin Levels and Serine 71 Phosphorylation in the Control of Cell-Matrix Adhesions, Migration Speed, and Shape of Transformed Human Fibroblasts
KTH, School of Engineering Sciences (SCI), Applied Physics, Cellular Biophysics.
KTH, School of Engineering Sciences (SCI), Applied Physics.
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2017 (English)In: CELLS, ISSN 2073-4409, Vol. 6, no 1, article id 2Article in journal (Refereed) Published
Abstract [en]

Metastasizing tumor cells show increased expression of the intermediate filament (IF) protein vimentin, which has been used to diagnose invasive tumors for decades. Recent observations indicate that vimentin is not only a passive marker for carcinoma, but may also induce tumor cell invasion. To clarify how vimentin IFs control cell adhesions and migration, we analyzed the nanoscale (30-50 nm) spatial organization of vimentin IFs and cell-matrix adhesions in metastatic fibroblast cells, using three-color stimulated emission depletion (STED) microscopy. We also studied whether wild-type and phospho-deficient or -mimicking mutants of vimentin changed the size and lifetime of focal adhesions (FAs), cell shape, and cell migration, using live-cell total internal reflection imaging and confocal microscopy. We observed that vimentin exists in fragments of different lengths. Short fragments were mostly the size of a unit-length filament and were mainly localized close to small cell-matrix adhesions. Long vimentin filaments were found in the proximity of large FAs. Vimentin expression in these cells caused a reduction in FAs size and an elongated cell shape, but did not affect FA lifetime, or the speed or directionality of cell migration. Expression of a phospho-mimicking mutant (S71D) of vimentin increased the speed of cell migration. Taken together, our results suggest that in highly migratory, transformed mesenchymal cells, vimentin levels control the cell shape and FA size, but not cell migration, which instead is linked to the phosphorylation status of S71 vimentin. These observations are consistent with the possibility that not only levels, but also the assembly status of vimentin control cell migration.

Place, publisher, year, edition, pages
MDPI AG , 2017. Vol. 6, no 1, article id 2
Keywords [en]
focal adhesions, vimentin, cell migration, total internal reflection (TIRF) microscopy, stimulated emission depletion (STED) microscopy
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:kth:diva-221038DOI: 10.3390/cells6010002ISI: 000418787000001Scopus ID: 2-s2.0-85050579240OAI: oai:DiVA.org:kth-221038DiVA, id: diva2:1173312
Funder
Swedish Cancer Society
Note

QC 20180112

Available from: 2018-01-12 Created: 2018-01-12 Last updated: 2018-10-16Bibliographically approved

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Coceano, GiovannaTesta, Ilaria

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