First Author | Batlle E | Year | 2005 |
Journal | Nature | Volume | 435 |
Issue | 7045 | Pages | 1126-30 |
PubMed ID | 15973414 | Mgi Jnum | J:99366 |
Mgi Id | MGI:3582031 | Doi | 10.1038/nature03626 |
Citation | Batlle E, et al. (2005) EphB receptor activity suppresses colorectal cancer progression. Nature 435(7045):1126-30 |
abstractText | 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. |