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Título: | In-depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer |
Autor: | Garranzo Asensio, María; Rodríguez-Cobos, Javier; San Millán, Coral; Povés, Carmen; Fernandez-Aceñero, M. Jesús; Pastor-Morate, Daniel CSIC; Viñal, David; Montero-Calle, Ana; Solís-Fernández, Guillermo; Cerón, María Ángeles; Gamez-Chiachio, Manuel CSIC ORCID; Rodríguez, Nuria CSIC ORCID; Guzmán-Aránguez, Ana I.; Barderas, Rodrigo CSIC ORCID; Domínguez, Gemma | Palabras clave: | ΔNp73 effectors Colorectal cancer In-depth proteomics Lymphangiogenesis Secretome |
Fecha de publicación: | jul-2022 | Citación: | Molecular Oncology 16(14): 2672-2692 (2022) | Resumen: | 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. | Versión del editor: | http://dx.doi.org/10.1002/1878-0261.13228 | URI: | http://hdl.handle.net/10261/340740 | DOI: | 10.1002/1878-0261.13228 | ISSN: | 1878-0261 |
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In-depth proteomics_Garranzo_PV_Art2022.pdf | 1,92 MB | Adobe PDF | Visualizar/Abrir |
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