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Genes Dev. 2007 Jun 1;21(11):1367-81. Epub 2007 May 17.

Autophagy suppresses tumor progression by limiting chromosomal instability.

Author information

1
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

Erratum in

  • Genes Dev. 2007 Jul 1;21(13):1701.

Abstract

Autophagy is a bulk degradation process that promotes survival under metabolic stress, but it can also be a means of cell death if executed to completion. Monoallelic loss of the essential autophagy gene beclin1 causes susceptibility to metabolic stress, but also promotes tumorigenesis. This raises the paradox that the loss of a survival pathway enhances tumor growth, where the exact mechanism is not known. Here, we show that compromised autophagy promoted chromosome instability. Failure to sustain metabolism through autophagy was associated with increased DNA damage, gene amplification, and aneuploidy, and this genomic instability may promote tumorigenesis. Thus, autophagy maintains metabolism and survival during metabolic stress that serves to protect the genome, providing an explanation for how the loss of a survival pathway leads to tumor progression. Identification of this novel role of autophagy may be important for rational chemotherapy and therapeutic exploitation of autophagy inducers as potential chemopreventive agents.

PMID:
17510285
PMCID:
PMC1877749
DOI:
10.1101/gad.1545107
[Indexed for MEDLINE]
Free PMC Article

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