Rosier, M., Krstulović, A. orcid.org/0009-0008-6760-506X, Kim, H.R. et al. (7 more authors) (2024) The Vimentin-targeting drug ALD-R491 partially reverts the epithelial-to-mesenchymal transition and vimentin interactome of lung cancer cells. Cancers, 17 (1). 81.
Abstract
Background: The epithelial-to-mesenchymal transition (EMT) is a common feature in early cancer invasion. Increased vimentin is a canonical marker of the EMT; however, the role of vimentin in EMT remains unknown. Methods: To clarify this, we induced EMT in lung cancer cells with TGF-β1, followed by treatment with the vimentin-targeting drug ALD-R491, live-cell imaging, and quantitative proteomics. Results: We identified 838 proteins in the intermediate filament fraction of cells. TGF-β1 treatment increased the proportion of vimentin in this fraction and the levels of 24 proteins. Variants of fibronectin showed the most pronounced increase (137-fold), followed by regulators of the cytoskeleton, cell motility, and division, such as the mRNA-splicing protein SON. TGF-β1 increased cell spreading and cell migration speed, and changed a positive correlation between cell migration speed and persistence to negative. ALD-R491 reversed these mesenchymal phenotypes to epithelial and the binding of RNA-binding proteins, including SON. Conclusions: These findings present many new interactors of intermediate filaments, describe how EMT and vimentin filament dynamics influence the intermediate filament interactome, and present ALD-R491 as a possible EMT-inhibitor. The observations support the hypothesis that the dynamic turnover of vimentin filaments and their interacting proteins govern mesenchymal cell migration, EMT, cell invasion, and cancer metastasis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | vimentin intermediate filaments; vimentin interactome; extracellular matrix; epithelial-to-mesenchymal transition; TGF-β1; cell migration; carcinoma; lung cancer |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > School of Chemical, Materials and Biological Engineering |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Jan 2025 13:00 |
Last Modified: | 13 Jan 2025 13:00 |
Published Version: | https://doi.org/10.3390/cancers17010081 |
Status: | Published |
Publisher: | MDPI AG |
Refereed: | Yes |
Identification Number: | 10.3390/cancers17010081 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221408 |