Autophagy regulates the survival of cells with chromosomal instability
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Dawei Liu1, Zeeshan Shaukat1, Tianqi Xu2, Donna Denton2, Robert Saint3, Stephen Gregory1
1Department of Genetics, University of Adelaide, Adelaide, SA, Australia
2Centre for Cancer Biology, University of South Australia, Adelaide, SA, Australia
3Flinders University, Adelaide, SA, Australia
Stephen Gregory, email: [email protected]
Keywords: chromosomal instability, autophagy, mitophagy, parkin, drosophila
Received: October 08, 2015 Accepted: August 21, 2016 Published: August 31, 2016
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.
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