Loss of primary cilia promotes inflammation and carcinogenesis.

Autor: Paul C; Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Label 'Equipe FRM', Montpellier, France., Tang R; Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Label 'Equipe FRM', Montpellier, France., Longobardi C; Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Label 'Equipe FRM', Montpellier, France.; Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Lattanzio R; Department of Innovative Technologies in Medicine & Dentistry, Center for Advanced Studies and Technology (CAST), 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Eguether T; Centre de Recherche Saint Antoine, Sorbonne Université, INSERM, APHP, Paris, France., Turali H; Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Label 'Equipe FRM', Montpellier, France., Bremond J; Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Label 'Equipe FRM', Montpellier, France., Maurizy C; Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Label 'Equipe FRM', Montpellier, France., Gabola M; Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Label 'Equipe FRM', Montpellier, France., Poupeau S; Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Label 'Equipe FRM', Montpellier, France., Turtoi A; Tumor Microenvironment and Resistance to Treatment Laboratory, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France., Denicolai E; Cancer Research Center of Marseille (CRCM), Laboratory of Predictive Oncology, Inserm U1068 - CNRS UMR7258 - University of Aix-Marseille UM105 - Paoli Calmettes Institute (IPC), Label 'Ligue contre le cancer', Marseille, France., Cufaro MC; Department of Innovative Technologies in Medicine & Dentistry, Center for Advanced Studies and Technology (CAST), 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Svrcek M; Department of Pathology, AP-HP, Hôpital Saint-Antoine, Sorbonne Université, Paris, France., Seksik P; Centre de Recherche Saint Antoine, Sorbonne Université, INSERM, APHP, Paris, France., Castronovo V; Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, Belgium., Delvenne P; Cancer Research Center of Marseille (CRCM), Laboratory of Predictive Oncology, Inserm U1068 - CNRS UMR7258 - University of Aix-Marseille UM105 - Paoli Calmettes Institute (IPC), Label 'Ligue contre le cancer', Marseille, France.; Department of Pathology, University Hospital (CHU), University of Liège, Liège, Belgium., de Laurenzi V; Department of Innovative Technologies in Medicine & Dentistry, Center for Advanced Studies and Technology (CAST), 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Da Costa Q; Cancer Research Center of Marseille (CRCM), Laboratory of Predictive Oncology, Inserm U1068 - CNRS UMR7258 - University of Aix-Marseille UM105 - Paoli Calmettes Institute (IPC), Label 'Ligue contre le cancer', Marseille, France., Bertucci F; Cancer Research Center of Marseille (CRCM), Laboratory of Predictive Oncology, Inserm U1068 - CNRS UMR7258 - University of Aix-Marseille UM105 - Paoli Calmettes Institute (IPC), Label 'Ligue contre le cancer', Marseille, France., Lemmers B; Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Label 'Equipe FRM', Montpellier, France., Pieragostino D; Department of Innovative Technologies in Medicine & Dentistry, Center for Advanced Studies and Technology (CAST), 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Mamessier E; Cancer Research Center of Marseille (CRCM), Laboratory of Predictive Oncology, Inserm U1068 - CNRS UMR7258 - University of Aix-Marseille UM105 - Paoli Calmettes Institute (IPC), Label 'Ligue contre le cancer', Marseille, France., Janke C; Institut Curie, Paris Sciences et Lettres (PSL) Research University, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 3348, Label 'Equipe FRM', Orsay, France.; Université Paris Sud, Université Paris-Saclay, CNRS UMR 3348, Orsay, France., Pinet V; Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Label 'Equipe FRM', Montpellier, France., Hahne M; Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Label 'Equipe FRM', Montpellier, France.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2022 Dec 06; Vol. 23 (12), pp. e55687. Date of Electronic Publication: 2022 Oct 25.
DOI: 10.15252/embr.202255687
Abstrakt: Primary cilia (PC) are important signaling hubs, and we here explored their role in colonic pathology. In the colon, PC are mostly present on fibroblasts, and exposure of mice to either chemically induced colitis-associated colon carcinogenesis (CAC) or dextran sodium sulfate (DSS)-induced acute colitis decreases PC numbers. We generated conditional knockout mice with reduced numbers of PC on colonic fibroblasts. These mice show increased susceptibility to CAC, as well as DSS-induced colitis. Secretome and immunohistochemical analyses of DSS-treated mice display an elevated production of the proinflammatory cytokine IL-6 in PC-deficient colons. An inflammatory environment diminishes PC presence in primary fibroblast cultures, which is triggered by IL-6 as identified by RNA-seq analysis together with blocking experiments. These findings suggest an activation loop between IL-6 production and PC loss. An analysis of PC presence on biopsies of patients with ulcerative colitis or colorectal cancer (CRC) reveals decreased numbers of PC on colonic fibroblasts in pathological compared with surrounding normal tissue. Taken together, we provide evidence that a decrease in colonic PC numbers promotes colitis and CRC.
(© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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