Cancer: Hijacking repair pathways to rewire cancer cells

Cancer cells reduce replication stress which can lead to cell death by inducing the expression of a subset of DNA repair genes whilst reducing genes involved in cell death. These findings are reported in Nature Communications this week, and provide further mechanistic insight into how cancer cells escape from stress generated by DNA mutations.

Mutations in the DNA repair gene FEN1 produce cells that have high levels of replication stress and altered numbers of chromosomes. Fen1 mutant mice have a tendancy to develop cancer and using cells from these mice Li Zheng, Binghui Shen and colleagues show that these cancer cells, with altered chromosome numbers, can overcome replication stress. They find that the cells increase the expression of genes involved in multiple DNA repair pathways including BRCA1 and p19ARF and these genes result in repair of damaged DNA. However, they note that at the same time genes involved in cell ageing and death were decreased in expression.

These findings reveal further molecular insights into how cancer cells with altered chromosome numbers and replication stress can manipulate cellular pathways to their advantage.