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Tytuł pozycji:

Mesalazine initiates an anti-oncogenic β-catenin / MUCDHL negative feed-back loop in colon cancer cells by cell-specific mechanisms.

Tytuł:
Mesalazine initiates an anti-oncogenic β-catenin / MUCDHL negative feed-back loop in colon cancer cells by cell-specific mechanisms.
Autorzy:
Bersuder E; Université de Strasbourg, Inserm, IRFAC / UMR-S1113, FHU ARRIMAGE, FMTS, Strasbourg, France.
Terciolo C; Université de Strasbourg, Inserm, IRFAC / UMR-S1113, FHU ARRIMAGE, FMTS, Strasbourg, France.
Lechevrel M; Université de Caen / Basse-Normandie, UFR de Médecine, EA 4652, F-14032 Caen, France.
Martin E; Université de Strasbourg, Inserm, IRFAC / UMR-S1113, FHU ARRIMAGE, FMTS, Strasbourg, France.
Quesnelle C; Université de Caen / Basse-Normandie, UFR de Médecine, EA 4652, F-14032 Caen, France.
Freund JN; Université de Strasbourg, Inserm, IRFAC / UMR-S1113, FHU ARRIMAGE, FMTS, Strasbourg, France.
Reimund JM; Université de Strasbourg, Inserm, IRFAC / UMR-S1113, FHU ARRIMAGE, FMTS, Strasbourg, France; Université de Caen / Basse-Normandie, UFR de Médecine, EA 4652, F-14032 Caen, France; Service Hépato-Gastroentérologie, Hôpitaux Universitaires de Strasbourg, F-67000 Strasbourg, France; Institut Hospitalo-Universitaire de Strasbourg, Hôpitaux Universitaires de Strasbourg, F-67000 Strasbourg, France. Electronic address: .
Gross I; Université de Strasbourg, Inserm, IRFAC / UMR-S1113, FHU ARRIMAGE, FMTS, Strasbourg, France. Electronic address: .
Źródło:
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2022 Feb; Vol. 146, pp. 112543. Date of Electronic Publication: 2021 Dec 20.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Publication: Paris : Editions Scientifiques Elsevier
Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982-
MeSH Terms:
Colonic Neoplasms*/drug therapy
Colonic Neoplasms*/genetics
Colonic Neoplasms*/metabolism
Colorectal Neoplasms*/genetics
Cadherin Related Proteins ; Cadherins/genetics ; Cadherins/metabolism ; Humans ; Mesalamine/pharmacology ; Wnt Signaling Pathway ; beta Catenin/metabolism
Contributed Indexing:
Keywords: 5-aminosalicylic acid; Adhesion; CDHR5; Colorectal neoplasm; Ulcerative Colitis; WNT pathway
Substance Nomenclature:
0 (CDHR5 protein, human)
0 (Cadherin Related Proteins)
0 (Cadherins)
0 (beta Catenin)
4Q81I59GXC (Mesalamine)
Entry Date(s):
Date Created: 20211220 Date Completed: 20220407 Latest Revision: 20220407
Update Code:
20240104
DOI:
10.1016/j.biopha.2021.112543
PMID:
34929577
Czasopismo naukowe
Chronic inflammation associated with intestinal architecture and barrier disruption puts patients with inflammatory bowel disease (IBD) at increased risk of developing colorectal cancer (CRC). Widely used to reduce flares of intestinal inflammation, 5-aminosalicylic acid derivatives (5-ASAs) such as mesalazine appear to also exert more direct mucosal healing and chemopreventive activities against CRC. The mechanisms underlying these activities are poorly understood and may involve the up-regulation of the cadherin-related gene MUCDHL (CDHR5). This atypical cadherin is emerging as a new actor of intestinal homeostasis and opposes colon tumorigenesis. Here, we showed that mesalazine increase mRNA levels of MUCDHL and of other genes involved in the intestinal barrier function in most intestinal cell lines. In addition, using gain / loss of function experiments (agonists, plasmid or siRNAs transfections), luciferase reporter genes and chromatin immunoprecipitation, we thoroughly investigated the molecular mechanisms triggered by mesalazine that lead to the up-regulation of MUCDHL expression. We found that basal transcription of MUCDHL in different CRC cell lines is regulated positively by CDX2 and negatively by β-catenin through a negative feed-back loop. However, mesalazine-stimulation of MUCDHL transcription is controlled by cell-specific mechanisms, involving either enhanced activation of CDX2 and PPAR-γ or repression of the β-catenin inhibitory effect. This work highlights the importance of the cellular and molecular context in the activity of mesalazine and suggests that its efficacy against CRC depends on the genetic alterations of transformed cells.
(Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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