%0 Journal Article
%A Garranzo Asensio, María
%A Rodríguez Cobos, Javier
%A San Millán, Coral
%A Poves, Carmen
%A Fernández Aceñero, María Jesús
%A Pastor Morate, Daniel
%A Viñal, David
%A Montero Calle, Ana
%A Solís Fernández, Guillermo
%A Ceron, María Ángeles
%A Gámez Chiachio, Manuel
%A Rodríguez Martín, Nuria
%A Guzmán Aránguez, Ana Isabel
%A Barderas Manchado, Rodrigo
%A Domínguez , Gemma
%T In-depth proteomics characterization of ΔNp73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer
%D 2022
%U https://hdl.handle.net/20.500.14352/129894
%X 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.
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