Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors

Abstract

Metastasis underlies the majority of cancer-related deaths yet remains poorly understood due, in part, to the lack of models in vivo. Here we show that expression of the EMT master inducer Snail in primary adult Drosophila intestinal tumors leads to the dissemination of tumor cells and formation of macrometastases. Snail drives an EMT in tumor cells, which, although retaining some epithelial markers, subsequently break through the basal lamina of the midgut, undergo a collective migration and seed polyclonal metastases. While metastases re-epithelialize over time, we found that early metastases are remarkably mesenchymal, discarding the requirement for a mesenchymal-to-epithelial transition for early stages of metastatic growth. Our results demonstrate the formation of metastases in adult flies, and identify a key role for partial-EMTs in driving it. This model opens the door to investigate the basic mechanisms underlying metastasis, in a powerful in vivo system suited for rapid genetic and drug screens.

Abstract

Modelling and visualizing tumor metastasis in Drosophila has been a challenge. Here, the authors show that constitutive expression of Sna in primary adult Drosophila intestinal tumors drives EMT and dissemination of tumor cells, induces collective cell migration and formation of polyclonal metastases.