2026-06-29T02:49:03Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1298942026-01-13T01:23:31Zcom_20.500.14352_14col_20.500.14352_15

In-depth proteomics characterization of ΔNp73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer Garranzo Asensio, María Rodríguez Cobos, Javier San Millán, Coral Poves, Carmen Fernández Aceñero, María Jesús Pastor Morate, Daniel Viñal, David Montero Calle, Ana Solís Fernández, Guillermo Ceron, María Ángeles Gámez Chiachio, Manuel Rodríguez Martín, Nuria Guzmán Aránguez, Ana Isabel Barderas Manchado, Rodrigo Domínguez , Gemma Colorectal 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. 2026-01-12T13:29:17Z 2026-01-12T13:29:17Z 2026-01-12T13:29:17Z 2022-07-16 journal article https://hdl.handle.net/20.500.14352/129894 XXXX-XXXX 10.1002/1878-0261.13228 eng Garranzo-Asensio M, Rodríguez-Cobos J, San Millán C, Poves C, Fernández-Aceñero MJ, Pastor-Morate D, Viñal D, Montero-Calle A, Solís-Fernández G, Ceron MÁ, Gámez-Chiachio M, Rodríguez N, Guzmán-Aránguez A, Barderas R, Domínguez G. In-depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer. Mol Oncol. 2022 Jul;16(14):2672-2692. doi: 10.1002/1878-0261.13228. Epub 2022 Jun 7. PMID: 35586989; PMCID: PMC9298678. http://creativecommons.org/licenses/by-sa/4.0/ open access Attribution-ShareAlike 4.0 International PubMed