title: Autophagy regulates the survival of cells with chromosomal instability.
abstract: Chromosomal instability (CIN) refers to genomic instability in which cells have gained or lost chromosomes or chromosomal fragments. A high level of CIN is common in solid tumours and is associated with cancer drug resistance and poor prognosis. The impact of CIN-induced stress and the resulting cellular responses are only just beginning to emerge. Using proliferating tissue in Drosophila as a model, we found that autophagy is activated in CIN cells and is necessary for their survival. Specifically, increasing the removal of defective mitochondria by mitophagy is able to lower levels of reactive oxygen species and the resultant cellular damage that is normally seen in CIN cells. In response to DNA damage, CIN is increased in a positive feedback loop, and we found that increasing autophagy by Tor depletion could decrease the level of CIN in proliferating cells. These findings underline the importance of autophagy control in the development of CIN tumours.
authors: Department of Genetics, University of Adelaide, Adelaide, SA, Australia.
authors: Dawei
authors: D
authors: Liu
authors: Department of Genetics, University of Adelaide, Adelaide, SA, Australia.
authors: Zeeshan
authors: Z
authors: Shaukat
authors: Centre for Cancer Biology, University of South Australia, Adelaide, SA, Australia.
authors: Tianqi
authors: T
authors: Xu
authors: Centre for Cancer Biology, University of South Australia, Adelaide, SA, Australia.
authors: Donna
authors: D
authors: Denton
authors: Flinders University, Adelaide, SA, Australia.
authors: Robert
authors: R
authors: Saint
authors: Department of Genetics, University of Adelaide, Adelaide, SA, Australia.
authors: Stephen
authors: S
authors: Gregory
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D049109:Cell Proliferation; D043171:Chromosomal Instability; D002875:Chromosomes / Q000648:ultrastructure; D004249:DNA Damage; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000378:metabolism; D004351:Drug Resistance; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D011379:Prognosis; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D017382:Reactive Oxygen Species; D044767:Ubiquitin-Protein Ligases; C487430:park protein, Drosophila
keywords: autophagy; chromosomal instability; drosophila; mitophagy; parkin