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

## TL;DR

A mutated form of the APC protein increases tissue tension, which hinders the removal of dead cells in epithelial tissues.

## Contribution

This study identifies APC as a modulator of tissue tension through the RhoA/ROCK pathway, linking APC mutations to impaired cell extrusion.

## Key findings

- APC truncation mutant increases epithelial tissue tension via the RhoA/ROCK pathway.
- Elevated tension disrupts apical cell extrusion in cultured cells and organoids.
- Reducing tissue tension pharmacologically rescues extrusion defects.

## Abstract

Tissue tension encompasses the mechanical forces exerted on solid tissues within animal bodies, originating from various sources such as cellular contractility, interactions with neighboring cells and the extracellular matrix. Emerging evidence indicates that an imbalance in such forces can influence structural organization, 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.