Letter abstract
Nature Genetics 39, 1403 - 1409 (2007)
Published online: 14 October 2007 | doi:10.1038/ng.2007.1
DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans
Julie Pinkston-Gosse1 & Cynthia Kenyon1
Cancer is an age-related disease, and inhibiting insulin/insulin-like growth factor 1 (IGF-1) signaling extends lifespan and increases tumor resistance in C. elegans and mammals. To investigate how the insulin/IGF-1 pathway couples these two processes, we analyzed putative transcriptional targets of the C. elegans FOXO transcription factor DAF-16, which promotes both longevity and tumor resistance. Twenty-nine of 734 genes tested influenced germline-tumor cell proliferation or p53-dependent apoptosis. About half of these genes also affected normal aging, thereby linking these two processes mechanistically. Many of these 29 genes are orthologs of known human tumor suppressors or oncogenes, suggesting that others may be as well. Our findings implicate nuclear-pore modification in p53-dependent cell death, because inhibiting nuclear-pore genes that are upregulated by DAF-16 blocks p53-dependent cell death in the tumor, but not normal, p53-independent, germline cell death.
- Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California 94158, USA.
Correspondence to: Cynthia Kenyon1 e-mail: ckenyon@biochem.ucsf.edu
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