Activated STAT regulates growth and induces competitive interactions independently of Myc, Yorkie, Wingless and ribosome biogenesis

Abstract

SUMMARYCell competition is a conserved mechanism that regulates organ size and shares properties with the early stages of cancer. In Drosophila, wing cells with increased Myc or with optimum ribosome function become supercompetitors that kill their wild-type neighbors (called losers) up to several cell diameters away. Here, we report that modulating STAT activity levels regulates competitor status. Cells lacking STAT become losers that are killed by neighboring wild-type cells. By contrast, cells with hyper-activated STAT become supercompetitors that kill losers located at a distance in a manner that is dependent on hid but independent of Myc, Yorkie, Wingless signaling, and of ribosome biogenesis. These results indicate that STAT, Wingless and Myc are major parallel regulators of cell competition, which may converge on signals that non-autonomously kill losers. As hyper-activated STATs are causal to tumorigenesis and stem cell niche occupancy, our results have therapeutic implications for cancer and regenerative medicine.

Cell competition, apoptosis and tumour development

“…2 in Moreno et al, 2002), which is implicated in stress-induced apoptosis in Drosophila (Stronach and Perrimon, 1999). This finding has been confirmed by more recent work (Brumby and Richardson, 2003, Martin et al, 2009, Menendez et al, 2010, Tamori et al, 2010, although the involvement of JNK has not been demonstrated in some cases (de la Cova et al, 2004, Rodrigues et al, 2012, Tyler et al, 2007.…”

Mechanisms and mechanics of cell competition in epithelia

“…Additional factors have been implicated in cell competition, including other growth regulators 19 , cell polarity [34][35][36][37] and steep differences in signalling activity 14,38,39 (FIG. 2).…”

“…Because of space constraints, here we do not discuss instances when steep differences in the activity of Wingless (which is the fly homologue of WNT), Decapentaplegic (Dpp; which is the fly homologue of transforming growth factor-β (TGFβ)) or JAK (Janus kinase)-STAT (signal transducer and activator of transcription) signalling trigger local apoptosis in a manner akin to cell competition 14,38,39 . Growth differential.…”

Apoptotic mechanisms during competition of ribosomal protein mutant cells: roles of the initiator caspases Dronc and Dream/Strica

“…9 Differences in Jak/Stat signaling, Wg signaling and cell adhesion are also reported to generate cell competition. [13][14][15] These findings suggest that cell competition arises from specific interactions between cells, rather than as a general consequence of differential growth.…”