Vimentin IFs as a Shield of Cellsagainst Doxorubicin

Abstract

Vimentin is a cytoskeleton protein of type III intermediate filaments (IFs) that is expressed in mesenchymal cells. Unlike other tissue-specific IF proteins vimentin may be found in different cell types. Thus, the expression of vimentin is a hallmark of an epithelial-to-mesenchymal transition (EMT), which is observed during early embryogenesis, wound healing, and the malignant transformation of various tumor cells. Besides the well-established function of vimentin IFs to provide the mechanical strength of the cells, we discovered that their interaction with mitochondria causes the decrease of their motility and the elevation of the mitochondrial membrane potential. These observations suggested an idea that vimentin could play a role in stabilization of mitochondria in the harsh conditions of chemotherapy and thus protect cancer cells against oxidative stress. Doxorubicin is used for treating a wide range of human tumors, including gastric carcinoma, breast carcinoma, leukemia, lung cancer, malignant lymphoma and others. Though it has been used clinically for over five decades, precise molecular pathways leading to the cancer cell death remain unexplored. However, various mechanisms have been proposed including topoisomerase inhibition, oxidative stress, and redox cycling of doxorubicin in mitochondria. Here, we analyze the recent data demonstrating vimentin’s role in cell protection against doxorubicin.