The focus of this unit is signal transduction and transcriptional control in cancer, focussed on three pathways, which are very frequently mutated in human cancer: the Ras signalling pathway (Bos), the APC-b-catenin-Tcf pathway (Clevers) and the PI-3-Kinase-PTEN-PKB-FoxO pathway (Burgering). Bos has in the past established the importance of Ras mutations in human cancers and since then studied the function of the Ras signalling pathway. Clevers co-discovered the b-catenin-Tcf interaction and made many contributions to our understanding of the role of this pathway in colorectal cancer. Burgering co-discovered the PI-3 kinase-PKB/Akt connection, and the connection of PKB with the control of the cell cycle through FoxO transcription factors. All three PI's are leading scientists in their field. UMCU will coordinate workpackage 5, aimed at proteomic dissection of oncogenic/ antioncogenic signalling pathways.

• Medema et al., 2000. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature. 404, 782-787.
• Kops et al., 2002. Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 419, 316-321.
• de Rooij et al., 1998. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396, 474-477.
• Batlle et al., 2002. Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell. 2002, 111, 251-263.
• van de Wetering et al., 2002. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 111, 241-250.