Batlle, E. and Bacani, J. and Begthel, H. and Jonkheer, S. and Gregorieff, A. and Born, M.van de and Malats, N. and Sancho, E. and Boon, E. and Pawson, T. and Gallinger, S. and Pals, S. and Clevers, J.C. (2005) EphB receptor activity suppresses colorectal cancer progression. Nature, 435(7045), 1126-1130. ISSN 14764687. doi: 10.1038/nature03626.
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Most sporadic colorectal cancers are initiated by activating Wnt pathway mutations, characterized by the stabilization of beta-catenin and constitutive transcription by the beta-catenin/T cell factor-4 (Tcf-4) complex. EphB guidance receptors are Tcf4 target genes that control intestinal epithelial architecture through repulsive interactions with Ephrin-B ligands. Here we show that, although Wnt signalling remains constitutively active, most human colorectal cancers lose expression of EphB at the adenoma-carcinoma transition. Loss of EphB expression strongly correlates with degree of malignancy. Furthermore, reduction of EphB activity accelerates tumorigenesis in the colon and rectum of Apc(Min/+) mice, and results in the formation of aggressive adenocarcinomas. Our data demonstrate that loss of EphB expression represents a critical step in colorectal cancer progression.
|Additional Information:||doi: 10.1038/nature03626|
|Deposited On:||13 Feb 2009 17:14|
|Last Modified:||10 Dec 2009 13:14|
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