Drosophila as a Model to Study the Link between Metabolism and Cancer

Cellular metabolism has recently been recognized as a hallmark of cancer. Investigating the origin and effects of the reprogrammed metabolism of tumor cells, and identifying its genetic mediators, will improve our understanding of how these changes contribute to disease progression and may suggest new approaches to therapy. Drosophila melanogaster is emerging as a valuable model to study multiple aspects of tumor formation and malignant transformation. In this review, we discuss the use of Drosophila as model to study how changes in cellular metabolism, as well as metabolic disease, contribute to cancer

The Drosophila Sterile-20 Kinase Slik Controls Cell Proliferation and Apoptosis during Imaginal Disc Development

Cell proliferation and programmed cell death are closely controlled during animal development. Proliferative stimuli generally also induce apoptosis, and anti-apoptotic factors are required to allow net cell proliferation. Genetic studies in Drosophila have led to identification of a number of genes that control both processes, providing new insights into the mechanisms that coordinate cell growth, proliferation, and death during development and that fail to do so in diseases of cell proliferation. We present evidence that the Drosophila Sterile-20 kinase Slik promotes cell proliferation and controls cell survival. At normal levels, Slik provides survival cues that prevent apoptosis. Cells deprived of Slik activity can grow, divide, and differentiate, but have an intrinsic survival defect and undergo apoptosis even under conditions in which they are not competing with normal cells for survival cues. Like some oncogenes, excess Slik activity stimulates cell proliferation, but this is compensated for by increased cell death. Tumor-like tissue overgrowth results when apoptosis is prevented. We present evidence that Slik acts via Raf, but not via the canonical ERK pathway. Activation of Raf can compensate for the lack of Slik and support cell survival, but activation of ERK cannot. We suggest that Slik mediates growth and survival cues to promote cell proliferation and control cell survival during Drosophila development

Complex collective states in a one-dimensional two-atom system

We consider a pair of identical two-level atoms interacting with a scalar field in one dimension, separated by a distance $x_{21}$. We restrict our attention to states where one atom is excited and the other is in the ground state, in symmetric or anti-symmetric combinations. We obtain exact collective decaying states, belonging to a complex spectral representation of the Hamiltonian. The imaginary parts of the eigenvalues give the decay rates, and the real parts give the average energy of the collective states. In one dimension there is strong interference between the fields emitted by the atoms, leading to long-range cooperative effects. The decay rates and the energy oscillate with the distance $x_{21}$. Depending on $x_{21}$, the decay rates will either decrease, vanish or increase as compared with the one-atom decay rate. We have sub- and super-radiance at periodic intervals. Our model may be used to study two-cavity electron wave-guides. The vanishing of the collective decay rates then suggests the possibility of obtaining stable configurations, where an electron is trapped inside the two cavities.Comment: 14 pages, 14 figures, submitted to Phys. Rev.

The chromatin remodeling BAP complex limits tumor-promoting activity of the Hippo pathway effector Yki to prevent neoplastic transformation in Drosophila epithelia

Switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are mutated in many human cancers. In this article, we make use of a Drosophila genetic model for epithelial tumor formation to explore the tumor suppressive role of SWI/SNF complex proteins. Members of the BAP complex exhibit tumor suppressor activity in tissue overexpressing the Yorkie (Yki) proto-oncogene, but not in tissue overexpressing epidermal growth factor receptor (EGFR). The Brahma-associated protein (BAP) complex has been reported to serve as a Yki-binding cofactor to support Yki target expression. However, we observed that depletion of BAP leads to ectopic expression of Yki targets both autonomously and non-autonomously, suggesting additional indirect effects. We provide evidence that BAP complex depletion causes upregulation of the Wingless (Wg) and Decapentaplegic (Dpp) morphogens to promote tumor formation in cooperation with Yki

Drosophila Melted Modulates FOXO and TOR Activity

SummaryThe insulin/PI3K signaling pathway controls both tissue growth and metabolism. Here, we identify Melted as a new modulator of this pathway in Drosophila. Melted interacts with both Tsc1 and FOXO and can recruit these proteins to the cell membrane. We provide evidence that in the melted mutant, TOR activity is reduced and FOXO is activated. The melted mutant condition mimics the effects of nutrient deprivation in a normal animal, producing an animal with 40% less fat than normal

HSPG Modification by the Secreted Enzyme Notum Shapes the Wingless Morphogen Gradient

AbstractThe secreted signaling protein Wingless acts as a morphogen to pattern the imaginal discs of Drosophila. Here we report identification of a secreted repressor of Wingless activity, which we call Notum. Loss of Notum function leads to increased Wingless activity by altering the shape of the Wingless protein gradient. When overexpressed, Notum blocks Wingless activity. Notum encodes a member of the α/β-hydrolase superfamily, with similarity to pectin acetylesterases. We present evidence that Notum influences Wingless protein distribution by modifying the heparan sulfate proteoglycans Dally-like and Dally. High levels of Wingless signaling induce Notum expression. Thus, Wingless contributes to shaping its own gradient by regulating expression of a protein that modifies its interaction with cell surface proteoglycans

The LRR Proteins Capricious and Tartan Mediate Cell Interactions during DV Boundary Formation in the Drosophila Wing

AbstractMechanisms to segregate cell populations play important roles in tissue patterning during animal development. Rhombomeres and compartments in the ectoderm and imaginal discs of Drosophila are examples in which initially homogenous populations of cells come to be separated by boundaries of lineage restriction. Boundary formation depends in part on signaling between the distinctly specified cell populations that comprise compartments and in part on formation of affinity boundaries that prevent intermingling of these cell populations. Here, we present evidence that two transmembrane proteins with leucine-rich repeats, known as Capricious and Tartan, contribute to formation of the affinity boundary between dorsal and ventral compartments during Drosophila wing development

Plant conversions and abatement technologies cannot prevent stranding of power plant assets in 2 °C scenarios

Continued fossil fuel development puts existing assets at risk of exceeding the capacity compatible with limiting global warming below 2 °C. However, it has been argued that plant conversions and new abatement technologies may allow for a smoother transition. We quantify the impact of future technology availability on the need for fossil fuel power plants to be stranded, i.e. decommissioned or underused. Even with carbon capture and storage (CCS) and bioenergy widely deployed in the future, a total of 267 PWh electricity generation (ten times global electricity production in 2018) may still be stranded. Coal-to-gas conversions could prevent 10-30 PWh of stranded generation. CCS retrofits, combined with biomass co-firing, could prevent 33-68 PWh. In contrast, lack of deployment of CCS or bioenergy could increase stranding by 69 or 45 percent respectively. Stranding risks remain under optimistic technology assumptions and even more so if CCS and bioenergy are not deployed at scale