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Stress Response, Aging, and Cancer Predisposition

The activity of FOXO transcription factors is associated with increased life span. Essers et al. (see the Perspective by Bowerman) find that in both Caenorhabditis elegans and mammalian cells, FOXO and β-catenin are associated in a protein complex. In C. elegans, β-catenin promotes the transcriptional activity of FOXO in response to oxidative stress. β-catenin mediates developmental effects of the wingless or Wnt pathway and is implicated in promoting excess cell proliferation in certain cancers. β-catenin's stimulation of FOXO, on the other hand, inhibits progression through the cell cycle. Thus, a critical balance between β-catenin signaling through FOXO or other transcription factors regulated by the Wnt pathway may influence stress responses, aging, and disposition to cancer. M. A. G. Essers, L. M. M. de Vries-Smits, N. Barker, P. E. Polderman, B. M. T. Burgering, H. C. Korswagen, Functional interaction between ß-catenin and FOXO in oxidative stress signaling. Science 308, 1181-1184 (2005). [Abstract] [Full Text] B. Bowerman, Oxidative stress and cancer: A β-catenin convergence. Science 308, 1119-1120 (2005). [Summary] [Full Text]