In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer
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 i...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-07-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13228 |
| _version_ | 1817970880646479872 |
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| author | María Garranzo‐Asensio Javier Rodríguez‐Cobos Coral San Millán Carmen Poves María Jesús Fernández‐Aceñero Daniel Pastor‐Morate David Viñal Ana Montero‐Calle Guillermo Solís‐Fernández María‐Ángeles Ceron Manuel Gámez‐Chiachio Nuria Rodríguez Ana Guzmán‐Aránguez Rodrigo Barderas Gemma Domínguez |
| author_facet | María Garranzo‐Asensio Javier Rodríguez‐Cobos Coral San Millán Carmen Poves María Jesús Fernández‐Aceñero Daniel Pastor‐Morate David Viñal Ana Montero‐Calle Guillermo Solís‐Fernández María‐Ángeles Ceron Manuel Gámez‐Chiachio Nuria Rodríguez Ana Guzmán‐Aránguez Rodrigo Barderas Gemma Domínguez |
| author_sort | María Garranzo‐Asensio |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T20:39:32Z |
| format | Article |
| id | doaj.art-234f5c92fcf7483793358afcfa781355 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-04-13T20:39:32Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-234f5c92fcf7483793358afcfa7813552022-12-22T02:30:54ZengWileyMolecular Oncology1574-78911878-02612022-07-0116142672269210.1002/1878-0261.13228In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancerMaría Garranzo‐Asensio0Javier Rodríguez‐Cobos1Coral San Millán2Carmen Poves3María Jesús Fernández‐Aceñero4Daniel Pastor‐Morate5David Viñal6Ana Montero‐Calle7Guillermo Solís‐Fernández8María‐Ángeles Ceron9Manuel Gámez‐Chiachio10Nuria Rodríguez11Ana Guzmán‐Aránguez12Rodrigo Barderas13Gemma Domínguez14Chronic Disease Programme (UFIEC) Instituto de Salud Carlos III Madrid SpainDepartamento de Bioquímica, Facultad de Medicina Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC‐UAM, IdiPAZ Madrid SpainDepartamento de Bioquímica, Facultad de Medicina Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC‐UAM, IdiPAZ Madrid SpainGastroenterology Unit Hospital Universitario Clínico San Carlos Madrid SpainSurgical Pathology Department Hospital Universitario Clínico San Carlos Madrid SpainDepartamento de Bioquímica, Facultad de Medicina Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC‐UAM, IdiPAZ Madrid SpainMedical Oncology Department Hospital Universitario La Paz Madrid SpainChronic Disease Programme (UFIEC) Instituto de Salud Carlos III Madrid SpainChronic Disease Programme (UFIEC) Instituto de Salud Carlos III Madrid SpainSurgical Pathology Department Hospital Universitario Clínico San Carlos Madrid SpainDepartamento de Bioquímica, Facultad de Medicina Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC‐UAM, IdiPAZ Madrid SpainMedical Oncology Department Hospital Universitario La Paz Madrid SpainDepartamento de Bioquímica y Biología Molecular, Facultad de Óptica y Optometría Universidad Complutense de Madrid SpainChronic Disease Programme (UFIEC) Instituto de Salud Carlos III Madrid SpainDepartamento de Bioquímica, Facultad de Medicina Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC‐UAM, IdiPAZ Madrid SpainColorectal 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.https://doi.org/10.1002/1878-0261.13228∆Np73 effectorscolorectal cancerin‐depth proteomicslymphangiogenesissecretome |
| spellingShingle | María Garranzo‐Asensio Javier Rodríguez‐Cobos Coral San Millán Carmen Poves María Jesús Fernández‐Aceñero Daniel Pastor‐Morate David Viñal Ana Montero‐Calle Guillermo Solís‐Fernández María‐Ángeles Ceron Manuel Gámez‐Chiachio Nuria Rodríguez Ana Guzmán‐Aránguez Rodrigo Barderas Gemma Domínguez In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer Molecular Oncology ∆Np73 effectors colorectal cancer in‐depth proteomics lymphangiogenesis secretome |
| title | In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer |
| title_full | In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer |
| title_fullStr | In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer |
| title_full_unstemmed | In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer |
| title_short | In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer |
| title_sort | in depth proteomics characterization of ∆np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis vasculogenesis and metastasis in colorectal cancer |
| topic | ∆Np73 effectors colorectal cancer in‐depth proteomics lymphangiogenesis secretome |
| url | https://doi.org/10.1002/1878-0261.13228 |
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