EphB receptor activity suppresses colorectal cancer progression

Eduard Batlle, Julinor Bacani, Harry Begthel, Suzanne Jonkeer, Alexander Gregorieff, Maaike Van De Born, Núria Malats, Elena Sancho, Elles Boon, Tony Pawson, Steven Gallinger, Steven Pals, Hans Clevers

Research output: Contribution to journalArticlepeer-review

351 Citations (Scopus)

Abstract

Most sporadic colorectal cancers are initiated by activating Wnt pathway mutations1, characterized by the stabilization of β-catenin and constitutive transcription by the β-catenin/T cell factor-4 (Tcf-4) complex2'3. EphB guidance receptors are Tcf4 target genes that control intestinal epithelial architecture through repulsive interactions with Ephrin-B ligands4'5. 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 ApcMin/+ 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.

Original languageEnglish
Pages (from-to)1126-1130
Number of pages5
JournalNature
Volume435
Issue number7045
DOIs
Publication statusPublished - 23 Jun 2005
Externally publishedYes

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