Mutant Vimentin Promotes Aggressive Breast Cancer Growth

Vimentin, a type III intermediate filament (IF) protein, is primarily expressed in mesenchymal cells, which give rise to connective tissue, blood vessels, and lymphatic tissue. Despite extensive research, its role in tumor growth and progression remains largely uncharted.

A research team led by Professor Ahmad Waseem and Dr. Saima Usman from the Centre for Oral Immunobiology and Regenerative Medicine, in collaboration with Professor Andrew Yeudall of the Dental College of Georgia at Augusta University, has uncovered how a subtle alteration in the vimentin protein can increase the aggressiveness of breast cancer.

Their study, published in eLife, found that replacing a single amino acid—cysteine with serine at position 328—disrupted vimentin’s interaction with the cell’s structural network. This seemingly minor mutation had profound effects, driving aggressive cancer-like behavior in breast cancer cells, including faster growth, increased migration and invasion, and reduced adhesion.

RNA sequencing further revealed that this mutant form of vimentin was associated with the upregulation of XIST, a non-coding RNA, suggesting a potential link between the mutation and gene expression changes that fuel cancer progression.

The researchers also discovered that breast cancer cells expressing mutant vimentin were able to grow independently of estrogen when injected into immunocompromised mice. Tumors in these mice exhibited high levels of cancer stem cell markers CD56 and CD20, indicating that the mutation may promote cancer stem cell-like behavior—a trait often linked to tumor progression, therapy resistance, and recurrence.

"Our study has identified a molecular interaction that, when disrupted, causes breast cancer cells to behave like cancer stem cells. Additionally, we’ve pinpointed a potential biomarker that could help detect these stem-like cells in breast cancer tissues. This is a critical step toward understanding how breast cancer develops and spreads, with possible implications for early diagnosis, prognosis, and targeted treatment strategies,"

Professor Ahmad Waseem, senior author of the study and professor at the Institute of Dentistry, Queen Mary University of London.