(Press-News.org) 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).
About Queen Mary
www.qmul.ac.uk
At Queen Mary University of London, we believe that a diversity of ideas helps us achieve the previously unthinkable.
Throughout our history, we’ve fostered social justice and improved lives through academic excellence. And we continue to live and breathe this spirit today, not because it’s simply ‘the right thing to do’ but for what it helps us achieve and the intellectual brilliance it delivers.
Our reformer heritage informs our conviction that great ideas can and should come from anywhere. It’s an approach that has brought results across the globe, from the communities of east London to the favelas of Rio de Janeiro.
We continue to embrace diversity of thought and opinion in everything we do, in the belief that when views collide, disciplines interact, and perspectives intersect, truly original thought takes form.
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Located in the historic city for which it is named and on regional campuses across the state, Augusta University is Georgia’s flagship health sciences and medical research university, home of the state’s Georgia Cyber Innovation and Training Center, and one of the country’s top universities for student success.
The university’s multi-disciplinary research enterprise and corporate, community and government partnerships propel frontier-expanding discovery and real-world solutions that address critical health, security, economic and societal concerns to advance and enrich the human experience.
With over 10,000 students guided by expert faculty and supportive mentors, Augusta University provides a personalized learning and discovery environment that creates a sense of belonging and encourages involvement and growth, combining critical and creative thinking with practical experiences and community engagement to prepare students from all backgrounds for lifelong success.
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Disruption of a single amino acid in a cellular protein makes breast cancer cells behave like stem cells
2025-02-11
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