The mechanical state of pre-tumoral epithelia controls subsequent Drosophila tumor aggressiveness

Abstract

Tumors evolve through the acquisition of increasingly aggressive traits associated with dysplasia. This progression is accompanied by alterations in tumor mechanical properties, especially through extracellular matrix remodeling. However, the contribution of pre-tumoral tissue mechanics to tumor aggressiveness remains poorly known in vivo. Here, we show that adherens junction tension in pre-tumoral tissues dictates subsequent tumor evolution in Drosophila. Increased cell contractility, observed in aggressive tumors before any sign of tissue overgrowth, proved sufficient to trigger dysplasia in normally hyperplastic tumors. In addition, high contractility precedes any changes in cell polarity and contributes to tumor evolution through cell death induction, which favors cell-cell junction weakening. Overall, our results highlight the need to re-evaluate the roles of tumoral cell death and identify pre-tumoral cell mechanics as an unsuspected early marker and key trigger of tumor aggressiveness.

Keywords: Crumbs; Drosophila; JNK; Syx7; Yorkie; aPKC; apoptosis; epithelial-mesenchymal transition; myosin II; tumor mechanics.