The Role of Abl Kinases in Lung Injury and Cancer

Abstract

Epithelial cells are the organism’s first defensive barrier to pathogens, toxins, and other noxious elements. Constant exposure to these elements requires exquisite control over the process of regeneration to ensure that damaged cells are constantly replenished while preventing overgrowth and maintaining organ size. Many of the mechanisms of proliferation and differentiation are exploited by sub-populations of cells following injury but also by tumor cells to allow uncontrolled growth and acquired resistance. In the lung, elegant studies have identified several putative stem cell populations contributing to the regeneration of lung epithelial cells following injury. However, despite the abundance of region specific lung stem/progenitor cells, a specific cellular source that can be activated in response to damage remains unknown. The studies presented here identify the Abl kinases as a potential cellular target in several progenitor cell types that can be targeted for efficient recovery following a variety lung injuries, including bacterial and viral pneumonia. Furthermore, by targeting some of the same pathways of de-differentiation cancer cells use to acquire resistance, Abl kinase inhibition promotes differentiation of primary lung cancer cells and renders them more susceptible to chemotherapy.