Keratin 1 as a cell-surface receptor in cancer

Keratins are fibrous proteins that take part in several important cellular functions, including the formation of intermediate filaments. In addition, keratins serve as epithelial cell markers, which has made their role in cancer progression, diagnosis, and treatment an important focus of research. Keratin 1 (K1) is a type II keratin whose structure is comprised of a coiled-coil central domain flanked by flexible, glycine-rich loops in the N- and C-termini. While the structure of cytoplasmic K1 is established, the structure of cell-surface K1 is not known. Several transformed cells, such as cancerous cells and cells that have undergone oxidative stress, display increased levels of overall and/or cell-surface K1 expression. Cell-surface keratins (CSKs) may be modified or truncated, and their role is yet to be fully elucidated. Current studies suggest that CSKs are involved in receptor-mediated endocytosis and immune evasion. In this Review, we discuss findings relating to K1 structure, overexpression, and cell-surface expression in the context of utilizing CSK1 as a receptor for targeted drug delivery to cancer cells, and other strategies to develop novel treatments for cancer.