title: Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and lymph node metastasis of carcinogen-induced colorectal tumors.
abstract: 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.
authors.affiliation: Institute of Molecular Immunology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schwitalla
authors.forename: Paul K
authors.initials: PK
authors.lastname: Ziegler
authors.forename: David
authors.initials: D
authors.lastname: Horst
authors.forename: Valentin
authors.initials: V
authors.lastname: Becker
authors.forename: Irina
authors.initials: I
authors.lastname: Kerle
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Begus-Nahrmann
authors.forename: André
authors.initials: A
authors.lastname: Lechel
authors.forename: K Lenhard
authors.initials: KL
authors.lastname: Rudolph
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.forename: Julia
authors.initials: J
authors.lastname: Slotta-Huspenina
authors.forename: Franz G
authors.initials: FG
authors.lastname: Bader
authors.forename: Olivia
authors.initials: O
authors.lastname: Prazeres da Costa
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
authors.forename: Alexander
authors.initials: A
authors.lastname: Meining
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.forename: Florian R
authors.initials: FR
authors.lastname: Greten
mesh_terms: D000236:Adenoma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002277:Carcinoma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D008198:Lymph Nodes / Q000473:pathology*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D059016:Tumor Microenvironment; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D002273:Carcinogens; D016159:Tumor Suppressor Protein p53