A truncation mutant of adenomatous polyposis coli (APC) impairs apical cell extrusion through elevated epithelial tissue tension

Abstract

ABSTRACTTissue tension encompasses the mechanical forces exerted on solid tissues within animal bodies, originating from various sources such as cellular contractility, interactions with neighbouring cells and the extracellular matrix. Emerging evidence indicates that an imbalance in tissue tension can influence structural organisation, homeostasis and potentially contribute to disease. For instance, heightened tissue tension can impede apical cell extrusion, leading to the retention of apoptotic or transformed cells. In this study, we investigate the potential role of adenomatous polyposis coli (APC) in modulating tissue tension. Our findings reveal that expression of an APC truncation mutant elevates epithelial tension via the RhoA/ROCK pathway. This elevation induces morphological alterations and hampers apoptotic cell extrusion in cultured epithelial cells and organoids, both of which could be mitigated by pharmacologically restoring the tissue tension. This raises the possibility that APC mutations may exert pathogenetic effects by altering tissue mechanics.