000048445 001__ 48445 000048445 005__ 20200221144148.0 000048445 0247_ $$2doi$$a10.18632/oncotarget.8678 000048445 0248_ $$2sideral$$a94372 000048445 037__ $$aART-2016-94372 000048445 041__ $$aeng 000048445 100__ $$aBosque, A. 000048445 245__ $$aComparative proteomics of exosomes secreted by tumoral jurkat t cells and normal human t cell blasts unravels a potential tumorigenic role for valosin-containing protein 000048445 260__ $$c2016 000048445 5060_ $$aAccess copy available to the general public$$fUnrestricted 000048445 5203_ $$aWe have previously characterized that FasL and Apo2L/TRAIL are stored in their bioactive form inside human T cell blasts in intraluminal vesicles present in multivesicular bodies. These vesicles are rapidly released to the supernatant in the form of exosomes upon re-activation of T cells. In this study we have compared for the first time proteomics of exosomes produced by normal human T cell blasts with those produced by tumoral Jurkat cells, with the objective of identify proteins associated with tumoral exosomes that could have a previously unrecognized role in malignancy. We have identified 359 and 418 proteins in exosomes from T cell blasts and Jurkat cells, respectively. Interestingly, only 145 (around a 40%) are common. The major proteins in both cases are actin and tubulin isoforms and the common interaction nodes correspond to these cytoskeleton and related proteins, as well as to ribosomal and mRNA granule proteins. We detected 14 membrane proteins that were especially enriched in exosomes from Jurkat cells as compared with T cell blasts. The most abundant of these proteins was valosin-containing protein (VCP), a membrane ATPase involved in ER homeostasis and ubiquitination. In this work, we also show that leukemic cells are more sensitive to cell death induced by the VCP inhibitor DBeQ than normal T cells. Furthermore, VCP inhibition prevents functional exosome secretion only in Jurkat cells, but not in T cell blasts. These results suggest VCP targeting as a new selective pathway to exploit in cancer treatment to prevent tumoral exosome secretion. 000048445 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/SAF2010$$9info:eu-repo/grantAgreement/ES/MICINN/SAF2013-48626-C2-1-R 000048445 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000048445 590__ $$a5.168$$b2016 000048445 591__ $$aONCOLOGY$$b44 / 217 = 0.203$$c2016$$dQ1$$eT1 000048445 591__ $$aCELL BIOLOGY$$b48 / 189 = 0.254$$c2016$$dQ2$$eT1 000048445 592__ $$a1.994$$b2016 000048445 593__ $$aOncology$$c2016$$dQ1 000048445 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000048445 700__ $$aDietz, L. 000048445 700__ $$aGallego-Lleyda, A. 000048445 700__ $$aSanclemente, M. 000048445 700__ $$0(orcid)0000-0003-4904-2319$$aIturralde, M.$$uUniversidad de Zaragoza 000048445 700__ $$0(orcid)0000-0003-2156-8378$$aNaval, J.$$uUniversidad de Zaragoza 000048445 700__ $$0(orcid)0000-0003-2872-4513$$aAlava, M.A.$$uUniversidad de Zaragoza 000048445 700__ $$0(orcid)0000-0003-3043-147X$$aMartínez-Lostao, L$$uUniversidad de Zaragoza 000048445 700__ $$aThierse, H.J. 000048445 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, A.$$uUniversidad de Zaragoza 000048445 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología 000048445 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000048445 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular 000048445 773__ $$g7 (2016), 29287-29305$$pONCOTARGET$$tOncotarget$$x1949-2553 000048445 8564_ $$s5032514$$uhttps://zaguan.unizar.es/record/48445/files/texto_completo.pdf$$yVersión publicada 000048445 8564_ $$s114743$$uhttps://zaguan.unizar.es/record/48445/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000048445 909CO $$ooai:zaguan.unizar.es:48445$$particulos$$pdriver 000048445 951__ $$a2020-02-21-13:07:10 000048445 980__ $$aARTICLE