A Single Amino Acid Change Makes Breast Cancer Cells More Aggressive

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 tumor growth and progression remains unexplored.  

A team of researchers led by Professor Ahmad Waseem and Dr. Saima Usman from the Centre for Oral Immunobiology and Regenerative Medicine, in collaboration with Andrew Yeudall, professor of oral biology in the Dental College of Georgia at Augusta University, have discovered how a small change in the vimentin protein can make breast cancer more aggressive. The research, published today in eLife, showed that modifying a specific amino acid cysteine to serine residue at position 328 in vimentin disrupted the protein’s interaction with the cell's structural network.  

Remarkably, the mutated vimentin induced aggressive cancer-like behavior 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 the 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 estrogen when injected into immunocompromised mice. The tumors 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 behavior that is often associated with tumor 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.” 

Reference: Usman S, Yeudall WA, Teh MT, Ghloum F, Tummala H, Waseem A. A single cysteine residue in vimentin regulates long non-coding RNA XIST to suppress epithelial-mesenchymal transition and stemness in breast cancer. eLife. 2025. doi: 10.7554/eLife.104191.1

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