<i>mthl1</i>, a potential <i>Drosophila</i> homologue of mammalian adhesion GPCRs, is involved in antitumor reactions to injected oncogenic cells in flies.

Abstract

Injection of OCs into adult male flies induces a strong transcriptomic response in the host flies featuring in particular genes encoding bona fide G coupled proteins, among which the gene for <i>methuselah</i> <i>like 1</i> is prominent. The injection is followed after a 3-d lag period, by the proliferation of the oncogenic cells. We hypothesized that through the product of <i>mthl1</i> the host might control, at least in part, this proliferation as a defense reaction. Through a combination of genetic manipulations of the <i>mthl1</i> gene (loss of function and overexpression of <i>mthl1</i>), we document that indeed this gene has an antiproliferative effect. Parallel injections of primary embryonic <i>Drosophila</i> cells or of various microbes do not exhibit this effect. We further show that <i>mthl1</i> controls the expression of a large number of genes coding for chemoreceptors and genes implicated in regulation of development. Of great potential interest is our observation that the expression of the mouse gene coding for the <i>adhesion G-protein-coupled receptor E1</i> (<i>Adgre1,</i> also known as <i>F4/80</i>), a potential mammalian homologue of <i>mthl1</i>, is significantly induced by B16-F10 melanoma cell inoculation 3 d postinjection in both the bone marrow and spleen (nests of immature and mature myeloid-derived immune cells), respectively. This observation is compatible with a role of this GPCR in the early response to injected tumor cells in mice.