Disruption of a single amino acid in a cellular protein makes breast cancer cells behave like stem cells

UNDER STRICT EMBARGO UNTIL TUESDAY 11 FEBRUARY 2025, 11am (UK time)  

Disruption of a single amino acid in a cellular protein makes breast cancer cells behave like stem cells  

Peer reviewed | Observational | Cells 

Changes to the intermediate filament (IF) protein, vimentin, were found to promote tumour growth by increasing cancer stemness in an oestrogen independent manner. Targeting vimentin and/or the long noncoding RNA (lncRNA) ‘XIST’ could be an effective therapeutic strategy for treating aggressive breast cancer. 

Vimentin is a type III intermediate filament (IF) protein normally expressed in cells that develop into connective tissue, blood vessels, and lymphatic tissue (mesenchymal cells). Despite being widely studied, its role in tumour growth and progression remains unexplored. 

A team of researchers at Queen Mary University of London have discovered how a small change in the vimentin protein can make breast cancer more aggressive. By modifying a specific amino acid cysteine to serine residue at position 328 in vimentin, they discovered that this mutation disrupted the protein’s interaction with the cell's structural network. Remarkably, the mutated vimentin induced aggressive cancer-like behaviour in breast cancer cells, including faster cell growth, migration, and invasion accompanied by reduced cell adhesion. RNA-sequencing further revealed that the presence of mutant vimentin was associated with upregulation of a non-coding RNA called XIST, suggesting a potential link between this mutation and gene expression changes that drive cancer progression. 

Researchers also found that mutant vimentin made breast cancer cells grow without depending on the hormone oestrogen when injected into immuno-compromised mice. The tumours in these mice showed high expression of cancer stem cell markers CD56 and CD20, suggesting a role for mutant vimentin in driving cancer stem cell-like behaviour that is often associated with tumour progression, therapeutic resistance and recurrence. 

Senior author Ahmad Waseem, Professor of Molecular and Cellular Oral Biology at the Institute of Dentistry, Queen Mary University of London, said: “Our study has discovered a molecular interaction that, when disrupted, causes breast cancer cells to behave like cancer stem cells. Additionally, we identified a potential biomarker that could help detect these stem-like cells in breast cancer tissues. This discovery represents an important step towards understanding how breast cancer develops and spreads, with potential implications for early diagnosis, prognosis, and targeted treatment strategies.” The lead author, Dr Saima Usman (HEC Fellow), did her PhD with Professor Waseem on this project. 

Co-author Andrew Yeudall, Professor of Oral Biology in the Dental College of Georgia at Augusta University, said: "The study will open new avenues for our understanding of cancer stem cell behaviour. For several years, Professor Waseem and I have been interested in studying the cancer-related roles of vimentin, which is induced in almost all later-stage tumours that have spread to other sites in the body and can be difficult to treat. We used MCF-7, a model breast epithelial cell line, partly because it is devoid of vimentin which therefore makes it easier to define functions related to specific vimentin mutations. Our observation that the cells became more aggressive, and that stem cell markers were induced, may unlock the door to new therapeutic approaches for breast and other cancers."  

ENDS 

NOTES TO EDITORS 

Other authors: 

Dr Saima Usman is currently an Assistant Professor in the National University of Medical Sciences (NUMS), Rawalpindi, Pakistan. She completed her PhD on this project. Dr Hemanth Tummala is a Senior Lecturer in the Blizard Institute, Queen Mary University of London. Muy-Teck Teh and Fatemah Ghloum are both from the Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Queen Mary University of London. 

Contact 

Honey Lucas 

Faculty Communications Officer – Medicine and Dentistry 

Queen Mary University of London 

Email: h.lucas@qmul.ac.uk or press@qmul.ac.uk 

Paper details:   

Saima Usman, et al. “A single cysteine residue in vimentin regulates long non-coding RNA XIST to suppress epithelial-mesenchymal transition and stemness in breast cancer.” Published in eLife. 

DOI: https://doi.org/10.7554/eLife.104191 
Available after publication at: TBC 

Under strict embargo until Tuesday 11 February 2025 at 11am (UK time). 

A copy of the paper is available upon request. 

Conflicts of interest: The authors declare that they have no competing interests. 

Funded by: The Higher Education Commission (HEC), Pakistan, provided Ph.D. studentships (to Saima Usman.). The Institute of Dentistry, Queen Mary University of London, waived the tuition fee that allowed Saima Usman to register for a PhD programme. Studies were funded in part by the National Institute of Dental and Craniofacial Research (5R01-DE024381 to Andrew Yeudall). 

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