The Vimentin-Targeting Drug ALD-R491 Partially Reverts the Epithelial-to-Mesenchymal Transition and Vimentin Interactome of Lung Cancer Cells
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture and Treatments
2.2. Antibodies and Cell Dyes
2.3. Western Blot
2.4. Immunoflourescence
2.5. Live-Cell Imaging
2.6. Image Analysis
2.7. Tracking Cell Migration
2.8. Monitoring Nuclear Division
2.9. Proteomic Analysis Using Label-Free Quantification Mass Spectrometry
2.10. Protein Identification, Relative Quantification, Bioinformatic Functional Profiling and Interaction Analysis
2.11. Statistical Analysis
3. Results
3.1. ALD-R491 Partially Reverses the Phenotypes of the Epithelial-to-Mesenchymal Transition
3.2. EMT-Increased Binding of Extracellular Matrix, Cell Motility, Cytokinesis, Cytoskeletal, and RNA-Binding Proteins to Vimentin, Is Partially Reversed by ALD-R491
4. Discussion
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Protein | Gene | Protein ID | Signalling Pathway | TGFβ1 vs. A549 Foldchange (p-Value) |
---|---|---|---|---|
Fibronectin;Anastellin;Ugl-Y1;Ugl-Y2;Ugl-Y3 | FN1 | P02751 | Integrin, Collagen, Fibrin | 137.19 (3.09 × 10−13) |
Transforming growth factor-β1-induced protein ig-h3 | TGF-Β1 | Q15582 | TGF-Β1, MAPK | 28.05 (1.33 × 10−10) |
Protein-glutamine gamma-glutamyltransferase 2 | TGM2 | P21980 | FN1, SPFN1, HSPB6 | 17.63 (2.09 × 10−18) |
5-nucleotidase | NT5E | P21589 | AMP- NAD- nucleotides | 6.92 (4.91 × 10−12) |
Aminopeptidase N | ANPEP | P15144 | an aminopeptidase | 5.58 (1.06 × 10−7) |
Neurabin-2 | PPP1R9B | Q96SB3 | F-actin, Rac, Dopamine D1 | 4.92 (0.000159) |
Zinc finger protein 185 | ZNF185 | O15231 | * Wnt | 4.86 (4.95 × 10−10) |
Drebrin 1 | DBN1 | Q16643 | * F-actin | 4.32 (1.88 × 10−10) |
Caldesmon | CALD1 | E9PGZ1 | F-actin,, myosin, calmodulin | 4.08 (5.49 × 10−10) |
SUN-domain-containing protein 2 | SUN2 | Q9UH99 | LINC complex | 3.92 (0.000905) |
SON | SON | P18583 | TUBG1, KATNB1, AURKB | 3.78 (0.0034) |
CTP synthase 1 | CTPS1 | A0A3B3IRI2 | CTP | 3.68 (3.42 × 10−5) |
Bcl-2-associated transcription factor 1 | BCLAF1 | A0A3B3ITZ9 | CCND1 mRNA | 3.48 (0.00372) |
Supervillin | SVIL | A0A6I8PIX7 | F-actin | 3.23 (0.000905) |
Protein PML | PML | P29590 | PML-NBs | 3.18 (0.000565) |
Protein disulfide-isomerase A4 | PDIA4 | A0A499FI48 | * HSP, ERO1 | 2.85 (0.000398) |
Transmembrane protein 43 | TMEM43 | Q9BTV4 | RNF26 | 2.62 (1.04 × 10−6) |
Uncharacterised protein C17orf85 | C17orf85 | Q53F19 | mRNA | 2.58 (0.00418) |
Thyroid-hormone-receptor-associated protein 3 | THRAP3 | A0A3B3ITZ9 | mRNA, DNA | 2.36 (0.00372) |
Alpha-actinin-1 | ACTN1 | P12814 | F-actin | 2.25 (3.66 × 10−10) |
LIM domain and actin-binding protein 1 | LIMA1 | Q9UHB6 | F-actin | 2.22 (0.000905) |
Kinesin-like protein 14 | KIF14 | Q15058 | Tubulin, CDKN1B | 2.11 (0.00102) |
Spectrin alpha chain, non-erythrocytic 1 | SPTAN1 | Q13813 | F-actin, Calmodulin | 2.06 (0.00151) |
Filamin-A | FLNA | P21333 | F-actin, SEMA3A | 2.01 (9.05 × 10−6) |
Protein | Gene | Protein ID | Signaling Pathway | TGFβ1 vs. A549 Fold Change (p-Value) |
---|---|---|---|---|
Protein SON | SON | P18583 | TUBG1, KATNB1, AURKB | −4.89 (0.00156) |
Aldehyde dehydrogenase, dimeric NADP-preferring | ALDH3A1 | P30838 | Aldehyde substrates | −2.62 (0.00257) |
RNA-binding protein FUS | FUS | P35637 | mRNA, DNA | −2.62 (0.00354) |
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Rosier, M.; Krstulović, A.; Kim, H.R.; Kaur, N.; Enakireru, E.M.; Symmes, D.; Dobra, K.; Chen, R.; Evans, C.A.; Gad, A.K.B. The Vimentin-Targeting Drug ALD-R491 Partially Reverts the Epithelial-to-Mesenchymal Transition and Vimentin Interactome of Lung Cancer Cells. Cancers 2025, 17, 81. https://doi.org/10.3390/cancers17010081
Rosier M, Krstulović A, Kim HR, Kaur N, Enakireru EM, Symmes D, Dobra K, Chen R, Evans CA, Gad AKB. The Vimentin-Targeting Drug ALD-R491 Partially Reverts the Epithelial-to-Mesenchymal Transition and Vimentin Interactome of Lung Cancer Cells. Cancers. 2025; 17(1):81. https://doi.org/10.3390/cancers17010081
Chicago/Turabian StyleRosier, Marieke, Anja Krstulović, Hyejeong Rosemary Kim, Nihardeep Kaur, Erhumuoghene Mary Enakireru, Deebie Symmes, Katalin Dobra, Ruihuan Chen, Caroline A. Evans, and Annica K. B. Gad. 2025. "The Vimentin-Targeting Drug ALD-R491 Partially Reverts the Epithelial-to-Mesenchymal Transition and Vimentin Interactome of Lung Cancer Cells" Cancers 17, no. 1: 81. https://doi.org/10.3390/cancers17010081
APA StyleRosier, M., Krstulović, A., Kim, H. R., Kaur, N., Enakireru, E. M., Symmes, D., Dobra, K., Chen, R., Evans, C. A., & Gad, A. K. B. (2025). The Vimentin-Targeting Drug ALD-R491 Partially Reverts the Epithelial-to-Mesenchymal Transition and Vimentin Interactome of Lung Cancer Cells. Cancers, 17(1), 81. https://doi.org/10.3390/cancers17010081