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

By O. Sansom, K. Reed, A. J. Hayes, H. Ireland, Hannah Brinkmann, I. P. Newton, E. Batlle, P. simon-Assmann, Hans Clevers, I. Nathke and 2 more. Genes & Development, 2004

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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 beta-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.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/37236231961bbe43aba79d9427d77033ac8278f7

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Citations in the corpus

Mutant p53 drives invasion by promoting integrin recycling. (2009, methodology): “Tumor number and size were then scored macroscopically and intestines fixed as previously described (Sansom et al., 2004).”
Transcription factor achaete scute-like 2 controls intestinal stem cell fate. (2009, background): “Proliferation of epithelial crypt cells is Wnt-dependent.”
The intestinal stem cell. (2008, background): “Third, mutations in the negative regulator of Wnt signaling APC, or expression of oncogenic forms of -catenin result in hyperproliferation of the epithelium (Harada et al. 1999; Romagnolo et al. 1999; Smits et al. 1999; Sansom et al. 2004; Andreu et al. 2005).”
YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response. (2014, background): “APC inactivation in conditional knockout mice is a paradigmmodel system to study the effects of Wnt signaling on the expansion of progenitor cells (Sansom et al., 2004).”
Wnt signaling in the intestinal epithelium: from endoderm to cancer. (2005, background): “Consistent with these results, mutations in the negative regulator of Wnt signaling APC, or overexpression of oncogenic forms of -catenin result in hyperproliferation of the epithelium (Nagase and Nakamura 1993; Oshima et al. 1995; Kinzler and Vogelstein 1996; Sansom et al. 2004).”