000095923 001__ 95923
000095923 005__ 20231108202259.0
000095923 0247_ $$2doi$$a10.1016/j.celrep.2020.107847
000095923 0248_ $$2sideral$$a118092
000095923 037__ $$aART-2020-118092
000095923 041__ $$aeng
000095923 100__ $$0(orcid)0000-0002-1861-5981$$aSantiago, L.$$uUniversidad de Zaragoza
000095923 245__ $$aExtracellular granzyme A promotes colorectal cancer development by enhancing gut inflammation
000095923 260__ $$c2020
000095923 5060_ $$aAccess copy available to the general public$$fUnrestricted
000095923 5203_ $$aIf not properly regulated, the inflammatory immune response can promote carcinogenesis, as evident in colorectal cancer (CRC). Aiming to gain mechanistic insight into the link between inflammation and CRC, we perform transcriptomics analysis of human CRC, identifying a strong correlation between expression of the serine protease granzyme A (GzmA) and inflammation. In a dextran sodium sulfate and azoxymethane (DSS/AOM) mouse model, deficiency and pharmacological inhibition of extracellular GzmA both attenuate gut inflammation and prevent CRC development, including the initial steps of cell transformation and epithelial-to-mesenchymal transition. Mechanistically, extracellular GzmA induces NF-κB-dependent IL-6 production in macrophages, which in turn promotes STAT3 activation in cultured CRC cells. Accordingly, colon tissues from DSS/AOM-treated, GzmA-deficient animals present reduced levels of pSTAT3. By identifying GzmA as a proinflammatory protease that promotes CRC development, these findings provide information on mechanisms that link immune cell infiltration to cancer progression and present GzmA as a therapeutic target for CRC.
000095923 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/SAF2017-83120-C2-1-R$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-1$$9info:eu-repo/grantAgreement/ES/DGA/B29$$9info:eu-repo/grantAgreement/ES/ISCIII/PI13-00864
000095923 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000095923 590__ $$a9.423$$b2020
000095923 591__ $$aCELL BIOLOGY$$b33 / 195 = 0.169$$c2020$$dQ1$$eT1
000095923 592__ $$a6.264$$b2020
000095923 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2020$$dQ1
000095923 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000095923 700__ $$0(orcid)0000-0001-8584-3979$$aCastro, Marta$$uUniversidad de Zaragoza
000095923 700__ $$aSanz-Pamplona, Rebeca
000095923 700__ $$0(orcid)0000-0001-6778-0636$$aGarzón, Marcela$$uUniversidad de Zaragoza
000095923 700__ $$0(orcid)0000-0002-3888-7036$$aRamírez-Labrada A.
000095923 700__ $$aTapia E.$$uUniversidad de Zaragoza
000095923 700__ $$aMoreno V.
000095923 700__ $$0(orcid)0000-0001-5573-6144$$aLayunta, E.$$uUniversidad de Zaragoza
000095923 700__ $$aGil-Gómez, G.
000095923 700__ $$aGarrido, M.
000095923 700__ $$aPeña R.
000095923 700__ $$0(orcid)0000-0001-7328-2094$$aLanuza, P.M.
000095923 700__ $$aComas L.$$uUniversidad de Zaragoza
000095923 700__ $$0(orcid)0000-0002-8731-4269$$aJaime-Sánchez, P.
000095923 700__ $$aUranga-Murillo, I.
000095923 700__ $$adel Campo, R.
000095923 700__ $$aPelegrín, P.
000095923 700__ $$aCamerer, E.
000095923 700__ $$0(orcid)0000-0003-3043-147X$$aMartínez-Lostao, L.$$uUniversidad de Zaragoza
000095923 700__ $$0(orcid)0000-0001-8567-4327$$aMuñoz, G.$$uUniversidad de Zaragoza
000095923 700__ $$aUranga, J.A.
000095923 700__ $$aAlcalde, A.
000095923 700__ $$0(orcid)0000-0001-6928-5516$$aGalvez, E.M.
000095923 700__ $$0(orcid)0000-0003-2280-9372$$aFerrández, A.$$uUniversidad de Zaragoza
000095923 700__ $$aBird, P.I.
000095923 700__ $$aMetkar, S.
000095923 700__ $$0(orcid)0000-0002-9730-2210$$aArias, M.A.
000095923 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J.$$uUniversidad de Zaragoza
000095923 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000095923 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000095923 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000095923 7102_ $$10$$2X$$aUniversidad de Zaragoza$$bServ.Gral. Apoyo Investigación$$cServicios. División Biomédica
000095923 7102_ $$11013$$2020$$aUniversidad de Zaragoza$$bDpto. Cirugía$$cÁrea Anatomía Patológica
000095923 773__ $$g32, 1 (2020), 107847 [23 pp.]$$pCell Reports$$tCell Reports$$x2211-1247
000095923 8564_ $$s5247116$$uhttps://zaguan.unizar.es/record/95923/files/texto_completo.pdf$$yVersión publicada
000095923 8564_ $$s159974$$uhttps://zaguan.unizar.es/record/95923/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000095923 909CO $$ooai:zaguan.unizar.es:95923$$particulos$$pdriver
000095923 951__ $$a2023-11-08-20:13:55
000095923 980__ $$aARTICLE