Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and lymph node metastasis of carcinogen-induced colorectal tumors.

Schwitalla S, Ziegler PK, Horst D, Becker V, Kerle I, Begus-Nahrmann Y, Lechel A, Rudolph KL, Langer R, Slotta-Huspenina J, Bader FG, Prazeres da Costa O, Neurath MF, Meining A, Kirchner T, Greten FR
Cancer Cell. 2013 23 (1): 93-106

PMID: 23273920 · DOI:10.1016/j.ccr.2012.11.014

Loss of p53 is considered to allow progression of colorectal tumors from the adenoma to the carcinoma stage. Using mice with an intestinal epithelial cell (IEC)-specific p53 deletion, we demonstrate that loss of p53 alone is insufficient to initiate intestinal tumorigenesis but markedly enhances carcinogen-induced tumor incidence and leads to invasive cancer and lymph node metastasis. Whereas p53 controls DNA damage and IEC survival during the initiation stage, loss of p53 during tumor progression is associated with increased intestinal permeability, causing formation of an NF-κB-dependent inflammatory microenvironment and the induction of epithelial-mesenchymal transition. Thus, we propose a p53-controlled tumor-suppressive function that is independent of its well-established role in cell-cycle regulation, apoptosis, and senescence.

Copyright © 2013 Elsevier Inc. All rights reserved.

MeSH Terms (13)

Adenoma Animals Carcinogens Carcinoma Colorectal Neoplasms Disease Models, Animal Lymph Nodes Mice Mutagenesis, Site-Directed Neoplasm Invasiveness Neoplasm Metastasis Tumor Microenvironment Tumor Suppressor Protein p53

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