Loss of primary cilia promotes inflammation and carcinogenesis

Autor: Conception Paul, Ruizhi Tang, Ciro Longobardi, Rossano Lattanzio, Thibaut Eguether, Hulya Turali, Julie Bremond, Chloé Maurizy, Monica Gabola, Sophie Poupeau, Andrei Turtoi, Emilie Denicolai, Maria Concetta Cufaro, Magali Svrcek, Philippe Seksik, Vincent Castronovo, Philippe Delvenne, Vincenzo de Laurenzi, Quentin Da Costa, François Bertucci, Bénédicte Lemmers, Damiana Pieragostino, Emilie Mamessier, Carsten Janke, Valérie Pinet, Michael Hahne
Přispěvatelé: Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunochimie des Régulations Cellulaires et des Interactions Virales (Inserm U354/Hôpital Saint-Antoine-APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Intégrité du génome, ARN et cancer, Institut Curie [Paris]-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Center of Experimental and Molecular Medicine, Graduate School
Rok vydání: 2022
Předmět:
Zdroj: EMBO Reports
EMBO Reports, 2022, ⟨10.15252/embr.202255687⟩
EMBO reports, 23(12):e55687. Wiley-Blackwell
ISSN: 1469-3178
1469-221X
Popis: International audience; 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.
Databáze: OpenAIRE
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