Cell exit during EMT is mechanically triggered independently of E-Cadherin loss

Abstract

Epithelial-to-mesenchymal transition (EMT) is a fundamental cell process with essential functions in tissue and organ formation during development but also metastasis during cancer progression. The shift between these two states is driven by evolutionary conserved transcription factors. Cell exit from the epithelium of origin is considered to be a mere consequence of progressive adhesion loss due to transcriptional repression of genes encoding molecules such as E-Cadherin or cell polarity regulators. Here we show in the Drosophila leg that, counterintuitively, adhesions (as well as cell polarity) are maintained during cell exit, while an apico-basal force is applied on E-Cadherin complexes in vivo. By combining a genetic screen, optogenetics and laser ablation experiments, we found that this pulling force originates from transient basal filopodia-like protrusions, formed as soon as cells start to exit. Finally, apical cell detachment requires -Spectrin activity, suggesting that the lateral cortex is required to efficiently transmit basal forces up to the apical cell pole. Our results indicate that, in a mature tissue, cell exit during EMT is a mechanically controlled process. Such a mechanism driving EMT without of E-Cadherin loss could fuel metastatic dissemination of collectively migrating cancer cells.