We investigate the cytoskeletal protein vimentin and its role in pulmonary health and disease. Vimentin is a type 3 intermediate filament that forms an intricate network within the cell. This dynamic, flexible network contributes to the motility and flexibility of cells that express the vimentin protein.
Vimentin is expressed in macrophages, where it contributes to the mechanical properties of these highly mobile cells. However, vimentin also plays a critical role in innate immunity signaling. Under certain conditions, vimentin is required for activation of the inflammasome, a multimolecular complex that produces inflammatory cytokines. Inflammation is necessary to control pathogens and other harmful agents, but it also causes injury to healthy tissue. In the absence of vimentin, inflammation and its associated tissue injury are greatly reduced. This raises intriguing clinical implications for the treatment of inflammatory diseases.
Induction of vimentin is a hallmark of epithelial-to-mesenchymal transition (EMT), a critical phase in the process of cancer metastasis. An epithelial-derived tumor cell undergoing EMT becomes more invasive and migratory, allowing it to penetrate the extracellular matrix and spread through the blood vessels to other organs. Vimentin also plays a role in tumorigenesis by upregulating the PI3K/Akt/mTOR signaling pathway, which promotes cell growth and proliferation. The involvement of vimentin in multiple stages of cancer development makes it a potential therapeutic target.