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

Schwitalla, Sarah; Ziegler, Paul K.; Horst, David; Becker, Valentin; Kerle, Irina; Begus-Nahrmann, Yvonne; Lechel, André; Rudolph, K. Lenhard; Langer, Rupert; Slotta-Huspenina, Julia; Bader, Franz G.; Prazeres da Costa, Olivia; Neurath, Markus F.; Meining, Alexander; Kirchner, Thomas; Greten, Florian R. (2013). Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and lymph node metastasis of carcinogen-induced colorectal tumors. Cancer cell, 23(1), pp. 93-106. Cell Press 10.1016/j.ccr.2012.11.014

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Langer, Rupert

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1535-6108

Publisher:

Cell Press

Language:

English

Submitter:

Andrea Arnold

Date Deposited:

07 Apr 2014 09:31

Last Modified:

05 Dec 2022 14:31

Publisher DOI:

10.1016/j.ccr.2012.11.014

PubMed ID:

23273920

URI:

https://boris.unibe.ch/id/eprint/45921

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