Mechanical state of pre-tumoral epithelia dictates subsequent tumour aggressiveness

Abstract

Tumours evolve through the acquisition of increasingly aggressive traits associated with dysplasia. This progression is accompanied by the alteration of tumour mechanical properties, especially through extracellular matrix remodelling. However, the contribution of intrinsic tumour cells mechanics to tumour aggressiveness remains unknown in vivo. Here we show that adherens junction tension in pre-tumoral tissues dictates subsequent tumour evolution. Increased cell contractility, observed in aggressive tumours before any sign of tissue overgrowth, proved sufficient to trigger dysplasia in normally hyperplastic tumours. Unexpectedly, high contractility contributes to tumour evolution through cell death induction which favours cell-cell junctions weakening. Overall, our results highlight the need to re-evaluate the roles of tumoral cell death, and identify pre-tumour cell mechanics as an unsuspected early marker and key trigger of tumour aggressiveness. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/594669v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1a677edorg.highwire.dtl.DTLVardef@b8940org.highwire.dtl.DTLVardef@15feebaorg.highwire.dtl.DTLVardef@13213ca_HPS_FORMAT_FIGEXP M_FIG C_FIG