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.

Life Extension

“…When flies are predisposed with a latent Ras1 oncogene, P. aeruginosa infection stimulates extreme stem cell proliferation and intestinal dysplasia, illustrating a synergy between bacterial infection and genetic predisposition (Apidianakis et al 2009). Furthermore, persistent bacterial infection activates the Imd-dTab2-dTak1 innate immune pathway, which synergizes with the Ras1 V12 oncogene to induce extracellular matrix degradation, basal invasion and hindgut cell dissemination to distant sites (Bangi et al 2012;Christofi and Apidianakis 2012).…”

Human pathogenic bacteria, fungi, and viruses inDrosophila

“…160 In addition, it may suppress the NFκB and JNK mediated innate immune response during wound infection but it may induce JNK signaling during intestinal infection to promote intestinal regeneration or tumor cell growth and dissemination. 38,161,162 P. aeruginosa actively limits the expression of Drosophila skeletal muscle genes at the site of wound infection and the expression of glutathione-S-transferase S1 (GstS1) in flies, a JNK-mediated response that is also conserved in mouse wound infections. 137 This wound site response is a resistance mechanism that inhibits bacterial growth and dissemination.…”

Fly foregut and transmission of microbes

“…flies- Nichols, 2005) and microbial pathogens, researchers, clinicians, and physicians must be aware of how these pathogens are obtained from the environment, how they remain/persist (Ma and Leulier, 2018;Obadia et al, 2017) within the vector/host, how they are transmitted to either our food products, our foods or to various hosts, and finally, how they might affect various tissues or organs of the host. Historically, and even recently, most pathogen research concerning adult dipterans has focused on the midgut (Lehane and Billingsley, 1996) and hindgut (Christofi and Apidianakis, 2013), ignoring the foregut. At the same time, some authors ( Junqueira et al, 2017;Tomberlin et al, 2017) present reviews and papers on the association between flies and their bacterial interactions, but focus mainly on identifying the microbes found in the guts of field collected flies with no reference as to where the microbes might be within the guts (i.e.…”