Birgitte Lane - Overview

Epithelia, the sheet tissues of the body, are the primary targets of carcinogenic changes. Nowhere is this more clear than in the skin. Epidermal cells are exposed to environmental carcinogens and a variety of extreme stresses, and their cell population is turned over frequently to avoid long-term damage and to keep the barrier intact. Within the epidermal keratinocyte cells, keratin intermediate filament proteins form networks of rope-like filaments running through the cytoplasm which help the cells to resist these stresses. We know this from findings, by ourselves and others, that mutations in different keratin intermediate filament genes cause a range of diverse epithelial fragility disorders, from skin blistering to a recent possible link with inflammatory bowel disease. The study of disease-causing mutations in keratins is one current area of research within our group.

It is not known why we need so many different intermediate filament genes, but the striking shifts in keratin gene expression that accompany normal differentiation suggest that the keratin cytoskeleton may impart different physical properties to epithelial cells in different body locations. Metastatic skin cancers, however, frequently begin to show altered keratin expression. It is becoming clear that keratins and other intermediate filaments can impact on disease processes in a number of ways. We are using drug-inducible mutant or wild-type keratin constructs in cultured cells and time-lapse filming of live cells with GFP-keratins, together with migration studies and stress assays, to provide further insight into the way keratins effect stress resistance. By measuring the stress resilience of cells and their ability to spread, change shape and migrate, and assessing the effect on these processes of altering the intermediate filament expression, a clearer picture can be built up of the many ways in which intermediate filaments influence cell function.