In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer. Issue 14 (7th June 2022)

• Record Type: Journal Article
• Authors: 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, Nuria; Guzmán‐Aránguez, Ana; Barderas, Rodrigo; Domínguez, Gemma
• Is Part Of: Molecular oncology. Volume 16:Issue 14(2022)
• Page Start: 2672
• Page End: 2692
• Publication Date: 2022-06-07
• Subjects: ∆Np73 effectors -- colorectal cancer -- in‐depth proteomics -- lymphangiogenesis -- secretome; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.13228
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : 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. Abstract : High‐density antibody microarrays and stable isotopic metabolic labeling allowed the identification of secreted dysregulated effectors by the ectopic ∆Np73 expression in HCT116 colorectal cancer (CRC) cells. After validating the dysregulation of the effectors by orthogonal techniques, an important association with lymphangiogenesis, vasculogenesis and CRC metastasis was found. Brain‐derived neurotrophic factor was validated by ELISA as potential biomarker of CRC.