Co-Operation between Aneuploidy and Metabolic Changes in Driving Tumorigenesis

Abstract

Alterations from the normal set of chromosomes are extremely common as cells progress toward tumourigenesis. Similarly, we expect to see disruption of normal cellular metabolism, particularly in the use of glucose. In this review, we discuss the connections between these two processes: how chromosomal aberrations lead to metabolic disruption, and vice versa. Both processes typically result in the production of elevated levels of reactive oxygen species, so we particularly focus on their role in mediating oncogenic changes.

Non-invasive, label-free optical analysis to detect aneuploidy within the inner cell mass of the preimplantation embryo

“…Aneuploidy results in altered cell metabolism in primary human fibroblasts and cancer cells (Newman, et al , 2019, Sheltzer, 2013, Warburg, 1956), yeast (Sheltzer, et al , 2011, Torres, et al , 2007), and human embryos (Fragouli, et al , 2015, Picton, et al , 2010). As metabolites and co-enzymes of metabolic pathways are naturally fluorescent, including nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide phosphate (NADPH) and flavins, there is potential to exploit this fluorescence as a non-invasive indicator of aneuploidy.…”

Genetic alterations associated with 18F-fluorodeoxyglucose positron emission tomography/computed tomography in head and neck squamous cell carcinoma

“…Chromosomal aberrations cause a wide range of gene alterations associated with metabolic disruption, a decrease in mitochondrial activity, and an elevated reactive oxygen species level, which in turn contributes to the Warburg effect. Changes in metabolism also increase the error rate in mitosis, causing genetic instability and vice versa [ 7 , 36 ].…”

Basic and Translational Models of Cooperative Oncogenesis

“…Through decades of research, we have gained much knowledge on key molecular events and processes involved in the formation of cancer, and much of this knowledge has stemmed from investigations using model organisms, such as the mouse and the vinegar fly, Drosophila melanogaster, in addition to in vitro cell line studies. In this Special Issue, we present a collection of original research papers on various aspects of cancer research utilising human cell lines [7,8], or in vivo using Drosophila as a model system [9,10], as well as reviews highlighting the Drosophila model organism in cancer research [11][12][13][14][15]. Drosophila is a particularly useful model organism for the study of cancer mechanisms, because it has a rapid life cycle and is genetically manipulatable and since cancer genes and signalling pathways are highly conserved between humans and Drosophila, and interactions between tumour cells and surrounding normal cells can be readily examined in Drosophila tissues [6,[16][17][18][19][20].…”

“…The reviews in this Special Issue highlight the power of using Drosophila as an in vivo model system to study various aspects of cancer research, from its application in the study of the function of specific genes/pathways in cancer [11,15], to understanding particular cellular processes in cancer [13,14], and for functional analyses of cancer Omics data [12]. Sechi et al [15] review the mechanisms of the Golgi phosphoprotein 3 (GOLPH3) oncogene in cancer, covering research on human cancer samples, in vitro cell line analyses and Drosophila in vivo analyses.…”

“…Cytonemes have recently been shown to be highly important in the development of glioblastoma and the associated neural degeneration that occurs in Drosophila models and also in the human disease [35], and there is accumulating evidence for their role in tumourigenesis in other cancer types. Newman and Gregory [13] review the connection between chromosomal aberrations (aneuploidy) and metabolic changes, highlighting the role of oxidative stress and particularly reactive oxygen species (ROS) in this process. Finally, Bangi [12] reviews how Drosophila can be utilised to functionally analyse the vast amount of human cancer Omics data that is currently being generated, in order to validate key genes/pathways that contribute to cancer, to build new models to interrogate cancer mechanisms, and to screen for novel cancer therapeutics.…”