Chromosomal instability causes sensitivity to metabolic stress

Zeeshan Shaukat, Dawei Liu, Amanda Choo, Rashid Hussain, Louise O'Keefe, Robert Richards, Robert Saint, Stephen Gregory

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4044-4055
Number of pages12
JournalOncogene
Volume34
Issue number31
DOIs
Publication statusPublished - 30 Jul 2015

Keywords

  • cancer metabolism
  • cell division
  • genomic instability

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