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In-depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer

dc.contributor.authorGarranzo-Asensio, Maria
dc.contributor.authorRodríguez-Cobos, Javier
dc.contributor.authorSan Millán, Coral
dc.contributor.authorPoves, Carmen
dc.contributor.authorFernández-Aceñero, María Jesús
dc.contributor.authorPastor-Morate, Daniel
dc.contributor.authorViñal, David
dc.contributor.authorMontero-Calle, Ana Maria
dc.contributor.authorSolis-Fernandez, Guillermo
dc.contributor.authorCeron, María-Ángeles
dc.contributor.authorGámez-Chiachio, Manuel
dc.contributor.authorRodríguez, Nuria
dc.contributor.authorGuzmán-Aránguez, Ana
dc.contributor.authorBarderas Manchado, Rodrigo
dc.contributor.authorDomínguez, Gemma
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)es_ES
dc.contributor.funderRochees_ES
dc.contributor.funderComunidad de Madrid (España)es_ES
dc.contributor.funderUnión Europea. Fondo Social Europeo (ESF/FSE)es_ES
dc.contributor.funderResearch Foundation - Flanderses_ES
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España)es_ES
dc.contributor.funderMinisterio de Asuntos Económicos y Transformación Digital (España)es_ES
dc.date.accessioned2022-11-17T10:36:58Z
dc.date.available2022-11-17T10:36:58Z
dc.date.issued2022-07
dc.description.abstractColorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. Alterations in proteins of the p53-family are a common event in CRC. ΔNp73, a p53-family member, shows oncogenic properties and its effectors are largely unknown. We performed an in-depth proteomics characterization of transcriptional control by ∆Np73 of the secretome of human colon cancer cells and validated its clinical potential. The secretome was analyzed using high-density antibody microarrays and stable isotopic metabolic labeling. Validation was performed by semiquantitative PCR, ELISA, dot-blot and western blot analysis. Evaluation of selected effectors was carried out using 60 plasma samples from CRC patients, individuals carrying premalignant colorectal lesions and colonoscopy-negative controls. In total, 51 dysregulated proteins were observed showing at least 1.5-foldchange in expression. We found an important association between the overexpression of ∆Np73 and effectors related to lymphangiogenesis, vasculogenesis and metastasis, such as brain-derived neurotrophic factor (BDNF) and the putative aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (EMAP-II)-vascular endothelial growth factor C-vascular endothelial growth factor receptor 3 axis. We further demonstrated the usefulness of BDNF as a potential CRC biomarker able to discriminate between CRC patients and premalignant individuals from controls with high sensitivity and specificity.es_ES
dc.description.peerreviewedes_ES
dc.description.sponsorshipThis study has been funded by Instituto de Salud Carlos III (ISCIII) through the project “PI18/00473” and co-funded by the European Union (FEDER funds) and Cátedra UAM-Roche en Medicina de Innovación to GD, and the Ramón y Cajal Programme of the MINECO, PI17CIII/00045 and PI20CIII/00019 research projects from AES-ISCIII to RB. MG-A and JR-C were supported by contracts of the Programa Operativo de Empleo Juvenil y la Iniciativa de Empleo Juvenil (YEI) with the participation of the Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid y del Fondo Social Europeo. AM-C FPU predoctoral contract is supported by the MECD. GS-F is a recipient of a predoctoral contract (grant num-ber 1193818N) supported by The Flanders Research Foundation (FWO).es_ES
dc.format.number14es_ES
dc.format.page2672-2692es_ES
dc.format.volume16es_ES
dc.identifier.citationMol Oncol. 2022 Jul;16(14):2672-2692.es_ES
dc.identifier.doi10.1002/1878-0261.13228es_ES
dc.identifier.e-issn1878-0261es_ES
dc.identifier.journalMolecular oncologyes_ES
dc.identifier.pubmedID35586989es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/15176
dc.language.isoenges_ES
dc.publisherWileyes_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F00473/ES/IDENTIFICACION DE LOS MECANISMOS IMPLICADOS EN LA DISEMINACION PERITONEAL DEL CANCER COLORRECTAL. PAPEL DE DELTANP73: IMPLICACIONES DIAGNOSTICAS, PRONOSTICAS Y TERAPEUTICAS./es_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/PI18/00473es_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/PI17CIII/00045es_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/PI20CIII/00019es_ES
dc.relation.publisherversionhttps://doi.org/10.1002/1878-0261.13228es_ES
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)es_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectΔNp73 effectorses_ES
dc.subjectColorectal canceres_ES
dc.subjectIn-depthproteomicses_ES
dc.subjectLymphangiogenesises_ES
dc.subjectSecretomees_ES
dc.subject.meshColorectal Neoplasmses_ES
dc.subject.meshLymphangiogenesises_ES
dc.subject.meshBrain-Derived Neurotrophic Factores_ES
dc.subject.meshHumanses_ES
dc.subject.meshProteomicses_ES
dc.subject.meshTumor Suppressor Protein p53es_ES
dc.subject.meshVascular Endothelial Growth Factor Aes_ES
dc.subject.meshVascular Endothelial Growth Factor Ces_ES
dc.titleIn-depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal canceres_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
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relation.isAuthorOfPublication3e80abe1-6578-487f-8201-f4c5ed3a674c
relation.isAuthorOfPublicationb08710f3-823c-4c5e-a191-699f1d89c5b1
relation.isAuthorOfPublicationdfb1f4f9-c8e8-4087-9db5-6477d4f154e4
relation.isAuthorOfPublication.latestForDiscovery840089f4-4c1e-4ac0-8214-93464312af82
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