title: Chromosomal instability causes sensitivity to metabolic stress.
abstract: Chromosomal INstability (CIN), a hallmark of cancer, refers to cells with an increased rate of gain or loss of whole chromosomes or chromosome parts. CIN is linked to the progression of tumors with poor clinical outcomes such as drug resistance. CIN can give tumors the diversity to resist therapy, but it comes at the cost of significant stress to tumor cells. To tolerate this, cancer cells must modify their energy use to provide adaptation against genetic changes as well as to promote their survival and growth. In this study, we have demonstrated that CIN induction causes sensitivity to metabolic stress. We show that mild metabolic disruption that does not affect normal cells, can lead to high levels of oxidative stress and subsequent cell death in CIN cells because they are already managing elevated stress levels. Altered metabolism is a differential characteristic of cancer cells, so our identification of key regulators that can exploit these changes to cause cell death may provide cancer-specific potential drug targets, especially for advanced cancers that exhibit CIN.
authors.affiliation: School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Adelaide, Australia.
authors.forename: Z
authors.initials: Z
authors.lastname: Shaukat
authors.affiliation: School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Adelaide, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.affiliation: School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Adelaide, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Choo
authors.affiliation: School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Adelaide, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Hussain
authors.affiliation: School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Adelaide, Australia.
authors.forename: L
authors.initials: L
authors.lastname: O'Keefe
authors.affiliation: School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Adelaide, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Richards
authors.affiliation: School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Adelaide, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Saint
authors.affiliation: School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, South Adelaide, Australia.
authors.forename: S L
authors.initials: SL
authors.lastname: Gregory
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics; D043171:Chromosomal Instability; D004249:DNA Damage; D004331:Drosophila melanogaster; D004625:Embryo, Nonmammalian; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D017382:Reactive Oxygen Species; D005978:Glutathione