Epithelial cell extrusion and its misregulation in disease

What links cell division to cell death in order to maintain constant epithelial cell densities? We found that mechanical forces control both processes: cell stretching triggers rapid cell division, whereas, crowding causes cell death by a process we call ‘epithelial extrusion’, in which cells fated to die are seamlessly squeezed out from epithelia. Extrusion is essential for maintaining correct epithelial cell densities. We are finding a growing number of diseases result from misregulation of extrusion. Excessive extrusion disrupts epithelial barrier, causing inflammation and infection hyper-sensitivity after an asthma attack. Conversely, oncogenic mutations hijack apical extrusion signaling and promote a class of aggressive tumors, which invade via a new mechanism—basal extrusion.