The fruit fly, Drosophila melanogaster, is used as a model organism to study disciplines ranging from fundamental genetics to the development of tissues and organs
Cancer cells also exhibit alterations in metabolic pathways that contribute to their survival. Rapidly proliferating cells have a high metabolic rate and suffer from low oxygen conditions (hypoxia). In epithelial tumors, this condition triggers the so-called angiogenic “switch” where the quiescent vascular network is induced to proliferate by the secretion of pro-angiogenic factors, such as VEGF (Vascular Endothelial Growth Factor) and FGF (Fibroblast Growth Factor) (Hida et al., 2018), allowing the formation of new vessels that penetrate into the tumor mass to supply oxygen and nutrients (Carmeliet and Jain, 2011). Cancers cells also exhibit a metabolic switch where they reprogram their metabolism to use an alternative and less abundant anabolic pathway to sustain their growth. In particular they switch from oxidative phosphorylation to anaerobic glycolysis, where glucose is used to produce lactate, through a process called the “Warburg effect” (Pavlova and Thompson, 2016; Vander Heiden and DeBerardinis, 2017). This metabolic switch is not yet completely characterized but is supported by the activation of oncogenes, including Myc that also activates glutaminolysis to fuel the TCA cycle with anaplerotic reactions to produce the intermediates necessary for cellular biosynthesis (Hsieh and Dang, 2016).
The last stage of tumorigenesis is represented by the invasive and metastatic capabilities of tumor cells to disrupt the apical-basal cell polarity, a process that is associated with the downregulation of cell-cell contact molecules and the release of metalloproteases (MMP1), lytic enzymes that degrade the extracellular matrix (ECM) allowing tumor cells to escape and colonize an environment that suites them and to acquire new oncogenic properties (Massague and Obenauf, 2016; Lambert et al., 2017). A variety of studies are now focused on how the tumor micro environment (TME), a specific niche composed of fibroblasts, lymphocytes and immune cells, that may shape pre-cancer cells for their progression into cancer cells and it may select the development of metastasis (Massague and Obenauf, 2016). Emergent evidence suggests also a key role for non-autonomous signals released by the cells composing the niche, particularly from cancer-associated fibroblasts (CAFs), that are essential to support the growth of cancer cells in this “new” metabolic environment