Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration

Owen J. Sansom; Karen R. Reed; Anthony J. Hayes; Heather Ireland; Hannah Brinkmann; Ian P. Newton; Eduard Batlle; Patricia Simon-Assmann; Hans Clevers; Inke S. Nathke; Alan R. Clarke; Douglas J. Winton

doi:10.1101/gad.287404

Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration

Owen J. Sansom
, Karen R. Reed
, Anthony J. Hayes
, Heather Ireland
, Hannah Brinkmann
, Ian P. Newton
, Eduard Batlle
, Patricia Simon-Assmann
, Hans Clevers
, Inke S. Nathke
, Alan R. Clarke (Lead / Corresponding author)
, Douglas J. Winton

Research output: Contribution to journal › Article › peer-review

711 Citations (Scopus)

Abstract

Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of ß-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a "crypt progenitor-like" phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.

Original language	English
Pages (from-to)	1385-1390
Number of pages	6
Journal	Genes & Development
Volume	18
Issue number	12
DOIs	https://doi.org/10.1101/gad.287404
Publication status	Published - 2004

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title = "Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration",

abstract = "Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of {\ss}-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a {"}crypt progenitor-like{"} phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.",

author = "Sansom, \{Owen J.\} and Reed, \{Karen R.\} and Hayes, \{Anthony J.\} and Heather Ireland and Hannah Brinkmann and Newton, \{Ian P.\} and Eduard Batlle and Patricia Simon-Assmann and Hans Clevers and Nathke, \{Inke S.\} and Clarke, \{Alan R.\} and Winton, \{Douglas J.\}",

year = "2004",

doi = "10.1101/gad.287404",

language = "English",

volume = "18",

pages = "1385--1390",

journal = "Genes \& Development",

issn = "0890-9369",

publisher = "Cold Spring Harbor Laboratory Press",

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TY - JOUR

T1 - Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration

AU - Sansom, Owen J.

AU - Reed, Karen R.

AU - Hayes, Anthony J.

AU - Ireland, Heather

AU - Brinkmann, Hannah

AU - Newton, Ian P.

AU - Batlle, Eduard

AU - Simon-Assmann, Patricia

AU - Clevers, Hans

AU - Nathke, Inke S.

AU - Clarke, Alan R.

AU - Winton, Douglas J.

PY - 2004

Y1 - 2004

N2 - Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of ß-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a "crypt progenitor-like" phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.

AB - Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of ß-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a "crypt progenitor-like" phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.

U2 - 10.1101/gad.287404

DO - 10.1101/gad.287404

M3 - Article

C2 - 15198980

SN - 0890-9369

VL - 18

SP - 1385

EP - 1390

JO - Genes & Development

JF - Genes & Development

IS - 12

ER -

Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration

Abstract

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