The Stearoyl-CoA Desaturase-1 (Desat1) in Drosophila cooperated with Myc to Induce Autophagy and Growth, a Potential New Link to Tumor Survival.

Chiara Paiardi,Zhasmine Mirzoyan,Andrea Vingiani,Federica Parisi,Paola Bellosta,Sheri Zola,Maria Pasini

doi:10.3390/genes8050131

Chiara Paiardi, Zhasmine Mirzoyan + Show 5 more

Open Access

https://doi.org/10.3390/genes8050131

Copy DOI

Abstract

Lipids are an important energy supply in our cells and can be stored or used to produce macromolecules during lipogenesis when cells experience nutrient starvation. Our proteomic analysis reveals that the Drosophila homologue of human Stearoyl-CoA desaturase-1 (Desat1) is an indirect target of Myc in fat cells. Stearoyl-CoA desaturases are key enzymes in the synthesis of monounsaturated fatty acids critical for the formation of complex lipids such as triglycerides and phospholipids. Their function is fundamental for cellular physiology, however in tumors, overexpression of SCD-1 and SCD-5 has been found frequently associated with a poor prognosis. Another gene that is often upregulated in tumors is the proto-oncogene c-myc, where its overexpression or increased protein stability, favor cellular growth. Here, we report a potential link between Myc and Desat1 to control autophagy and growth. Using Drosophila, we found that expression of Desat1, in metabolic tissues like the fat body, in the gut and in epithelial cells, is necessary for Myc function to induce autophagy a cell eating mechanism important for energy production. In addition, we observed that reduction of Desat1 affects Myc ability to induce growth in epithelial cells. Our data also identify, in prostatic tumor cells, a significant correlation between the expression of Myc and SCD-1 proteins, suggesting the existence of a potential functional relationship between the activities of these proteins in sustaining tumor progression.

Highlights

Cancer cells require an extensive supply of energy to grow, and when they are constrained by limited nutrients, they can reprogram metabolic pathways to allow for continued growth
Myc induces the expression of several components of lipid metabolism, including Desat1, whose activity was shown to be necessary for the ability of Myc to increase triglyceride levels and to control systemic growth and enhance animal survival in low nutrient conditions [7]
We previously reported that Myc overexpression in the fat body activates metabolic pathways allowing for the survival of animals in low nutrient starvation [7]; this prompted us to perform a proteomic analysis to identify novel proteins that contribute to maintaining the basal level of proteomic analysis to identify novel proteins that contribute to maintaining the basal level of metabolism in fat cells whenwhen nutrients are reduced

Summary

Introduction

Cancer cells require an extensive supply of energy to grow, and when they are constrained by limited nutrients, they can reprogram metabolic pathways to allow for continued growth. Myc overexpression during starvation activates a switch in cellular metabolism, triggering glycolytic flux and enhancing metabolic pathways, including glycolysis and alternative routes like glutamine signaling [7] This function of Myc is conserved in human and Drosophila cells, where it was shown to induce metabolic changes allowing cells of the wing imaginal discs to acquire a competitive behavior (winner cells) over wild-type loser cells in the presence of a fully activated p53 [9]. This behavior was demonstrated during the initial steps of tumorigenesis, when the overexpression of tumor-promoting genes (i.e., c-myc) in precancerous cells gives the cells a growth advantage (winners) and eliminates non-cancerous cells (losers) [10,11]

Methods

Results

Conclusion