Skin epithelial cells change their mechanics and proliferation upon Snail-mediated EMT signalling

Abstract

Skin cancer is the most commonly occurring cancer in the USA and Germany, and the fourth most common cancer worldwide. Snail-dependent epithelial-mesenchymal transition (EMT) was shown to initiate and promote skin cancer. Previous studies could show that EMT changes actin cortex regulation and cellular mechanics in epithelial cells of diverse tissue origin. However, in spite of its potentially high significance in the context of skin cancer, the effect of EMT on cellular mechanics, mitotic rounding and proliferation has not been studied in skin epithelial cells so far. In this work we show that TGF-{beta}-induced partial EMT results in a transformation of the mechanical phenotype of skin epithelial cells in a cell-cycle dependent manner. Concomitantly, we looked at EMT-induced changes of cell proliferation. While EMT decreases proliferation in 2D culture, we observed an EMT-induced boost of cellular proliferation when culturing cells as mechanically confined aggregates of skin epithelial cells. This proliferation boost was accompanied by enhanced mitotic rounding and composition changes of the actin cortex. We give evidence that observed EMT-induced changes depend on the EMT-upregulated transcription factor Snail. Overall, our findings indicate that EMT-induced changes of cellular mechanics might play a currently unappreciated role in EMT-induced promotion of skin tumor proliferation. Significance statementThis study describes how epithelial-mesenchymal transition (EMT) alters the actin cytoskeleton, cellular mechanics and proliferation in a benign tumor model of skin epithelial cells. We show that corresponding EMT-induced phenotypes depend on the signalling of the transcription factor Snail. Our findings suggest that EMT-induced changes of cellular mechanics and proliferation might play a currently under-appreciated role in EMT-induced promotion of skin tumors.