Ras-oncogenic Drosophila hindgut but not midgut cells use an inflammation-like program to disseminate to distant sites.

Abstract

The gastrointestinal tract is habitable by a variety of microorganisms and it is often a tissue inflicted by inflammation. Much discussion is raised in recent years about the role of microbiota in intestinal inflammation, but their role in intestinal cancer remains unclear. Here we discuss and extent our work on Drosophila melanogaster models of tumorigenesis and tumor cell invasion upon intestinal infection. In Drosophila midgut bacteria that cause enterocyte damage induce intestinal stem cell proliferation, which is diverted toward aberrant stem cell expansion upon oncogene expression to induce dysplastic tumors. In the hindgut though, oncogenes synergize with the innate immune response-not the bacterially mediated damage-to induce tumor cell invasion and dissemination to distant sites. Interestingly, our novel gene expression analysis of Drosophila hemocyte-like cells suggests commonalities with oncogenic hindgut cells in the innate immune response and the expression of matrix metalloproteinase 1 in response to bacterial infection.