Activation of Notch-1 signalling maintains the neoplastic phenotype in Ras-transformed cellsNature Medicine (2002)
AbstractTruncated Notch receptors have transforming activity in vitro and in vivo. However, the role of wild-type Notch signaling in neoplastic transformation remains unclear. Ras signaling is deregulated in a large fraction of human malignancies and is a major target for the development of novel cancer treatments. We show that oncogenic Ras activates Notch signaling and that wild-type Notch-1 is necessary to maintain the neoplastic phenotype in Ras-transformed human cells in vitro and in vivo. Oncogenic Ras increases levels and activity of the intracellular form of wild-type Notch-1, and upregulates Notch ligand Delta-1 and also presenilin-1, a protein involved in Notch processing, through a p38-mediated pathway. These observations place Notch signaling among key downstream effectors of oncogenic Ras and suggest that it might be a novel therapeutic target.
Publication DateSeptember, 2002
Citation InformationBarbara A. Osborne. "Activation of Notch-1 signalling maintains the neoplastic phenotype in Ras-transformed cells" Nature Medicine Vol. 8 Iss. 9 (2002)
Available at: http://works.bepress.com/barbara_osborne/66/