It was discovered that changes in the protein of the intermediate filament (IF), the vimentin, promote tumor growth by increasing the path of cancer independently of estrogen. Directing Vimentina and/or ‘Xist’ of Non -Coding RNA (LNCRNA) could be an effective therapeutic strategy to treat aggressive breast cancer.
Vimentin is an intermediate filament protein (IF) Type III that is normally expressed in cells that are developed in 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 from Queen Mary in London has discovered how a small change in vimentin protein can make breast cancer more aggressive. By modifying a specific amino acid cysteine to the serine residue in position 328 in vimentin, they discovered that this mutation interrupted the interaction of the protein with the structural network of the cell. Surprisingly, mutated vimentin induced aggressive cancer behavior in breast cancer cells, which include faster cell growth, migration and invasion accompanied by reduced cell adhesion. The RNA sequencing also revealed that the presence of mutant vimentin was associated with the positive regulation of an unbashed RNA called Xist, which suggests a potential link between this mutation and the changes in the gene expression that drive the progression of cancer.
The researchers also found that mutant vimentin caused breast cancer cells to grow without depending on estrogen hormone when injected into immunocompromised mice. The tumors in these mice showed a high expression of the CD56 and CD20 cancer stem cell markers, which suggests a role for mutant vimentin in conducting behavior similar to cancer stem cells that is often associated with progression tumor, therapeutic resistance and recurrence.
The main author Ahmad Waseem, professor of molecular and cellular oral biology at the Institute of Dentistry of the University of London of Queen Mary, said: “Our study has discovered a molecular interaction that, when interrupted, makes the cancer cells of Mama behave like cancer stem cells. Doctorate with Professor Waseem in this project.
The co -author Andrew Yeudall, professor of oral biology at the Georgia Dental College of the University of Augusta, said: “The study will open new ways for our understanding of the behavior of cancer stem cells. For several years, Professor Waseem and I We have been interested in studying the vimentin roles related to cancer, which is induced in almost all posterior stage tumors that have extended to other places in the body and can be difficult to treat. Vimentina, which makes it easier to define functions related to specific vimentin mutations.