# The directionality of collective cell delamination is governed by tissue architecture and cell adhesion in a Drosophila carcinoma model

## TL;DR

This study shows how tissue structure and cell adhesion control the direction in which cancer cells detach from tissues in a fruit fly model.

## Contribution

The study reveals how septate junctions and cell adhesion influence delamination direction in a Drosophila carcinoma model.

## Key findings

- Loss of septate junctions in RasV12-cells promotes collective delamination.
- Apical and basal delamination differ in cell identity and junctional remodeling.
- Tissue architecture and preferential adhesion regulate delamination direction.

## Abstract

Epithelial cells contact each other and the extracellular matrix via cell junctions, establishing mechanochemical barriers. During collective delamination, epithelia-derived tumors detach from the tissue with a directionality that dictates their malignancy. How cell junctions contribute to this process and how the directionality of delamination is regulated remains unknown. We used the Drosophila RasV12 carcinoma model and found that the loss of septate junctions in epithelial cells triggers apoptosis, whereas in RasV12-cells promotes collective delamination. We found that apical and basal delamination differ in cell identity, polarity, and junctional remodeling, occurring exclusively in squamous and pseudostratified epithelia, respectively. We performed mathematical simulations using a 2D agent-based model and found that tissue architecture and preferential adhesion between mutant cells and with wild-type neighbors regulate the directionality of delamination. Apical delamination initiates with cells constricting apically, emitting apical protrusions, and forming an apical neck via preferential adhesion to collectively detach from the tissue.

•Loss of septate junction integrity promotes apoptosis•Loss of septate junction integrity in RasV12-cells promotes delamination•Junctional remodeling and cell identity differ between apical and basal delamination•Preferential adhesion and tissue architecture regulate the directionality of delamination

Loss of septate junction integrity promotes apoptosis

Loss of septate junction integrity in RasV12-cells promotes delamination

Junctional remodeling and cell identity differ between apical and basal delamination

Preferential adhesion and tissue architecture regulate the directionality of delamination

Cancer; Cell biology