EphB receptor activity suppresses colorectal cancer progression.

E. Batlle; J. Bacani; H. Begthel; S. Jonkheer; A. Gregorieff; M.van de Born; N. Malats; E. Sancho; E. Boon; T. Pawson; S. Gallinger; S. Pals; J.C. Clevers

EphB receptor activity suppresses colorectal cancer progression.

E. Batlle, J. Bacani, H. Begthel, S. Jonkheer, A. Gregorieff, M.van de Born, N. Malats, E. Sancho, E. Boon, T. Pawson, S. Gallinger, S. Pals, J.C. Clevers

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

357 Citaten (Scopus)

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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.

Originele taal-2	Engels
Pagina's (van-tot)	1126-1130
Tijdschrift	Nature
Volume	435
Status	Gepubliceerd - 2005

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title = "EphB receptor activity suppresses colorectal cancer progression.",

abstract = "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.",

author = "E. Batlle and J. Bacani and H. Begthel and S. Jonkheer and A. Gregorieff and Born, {M.van de} and N. Malats and E. Sancho and E. Boon and T. Pawson and S. Gallinger and S. Pals and J.C. Clevers",

note = "doi: 10.1038/nature03626",

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TY - JOUR

T1 - EphB receptor activity suppresses colorectal cancer progression.

AU - Batlle, E.

AU - Bacani, J.

AU - Begthel, H.

AU - Jonkheer, S.

AU - Gregorieff, A.

AU - Born, M.van de

AU - Malats, N.

AU - Sancho, E.

AU - Boon, E.

AU - Pawson, T.

AU - Gallinger, S.

AU - Pals, S.

AU - Clevers, J.C.

N1 - doi: 10.1038/nature03626

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

M3 - Article

SN - 0028-0836

VL - 435

SP - 1126

EP - 1130

JO - Nature

JF - Nature

ER -

EphB receptor activity suppresses colorectal cancer progression.

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