DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans.

Authors: Pinkston-Gosse J; Kenyon C

Abstract: 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.

Keywords: Aging/*genetics; Animals; Caenorhabditis elegans/*genetics/growth & development/metabolism; Caenorhabditis elegans Proteins/antagonists & inhibitors/*genetics/metabolism; *Gene Expression Regulation, Developmental; Genes, Tumor Suppressor/physiology; Neoplasms/genetics/metabolism/*pathology; Oncogenes/physiology; RNA Interference; RNA, Helminth/genetics/metabolism; Receptor, Insulin/antagonists & inhibitors/genetics/metabolism; Signal Transduction; Survival Rate; Transcription Factors/antagonists & inhibitors/*genetics/metabolism; Transcription, Genetic
Journal: Nature genetics
Volume: 39
Issue: 11
Pages: 1403-9
Date: Oct. 16, 2007
PMID: 17934462
Select reference article to upload


Citation:

Pinkston-Gosse J, Kenyon C (2007) DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans. Nature genetics 39: 1403-9.


Study
Update (Admin) | Auto-Update

Comment on This Data Unit