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Silencing of adaptor protein 32 reduces / receptors expression and impairs gastrointestinal stromal tumors growth
Serrano-Candelas, Eva (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Ainsua-Enrich, Erola (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Navinés-Ferrer, Arnau (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Rodrigues, Paulo (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García-Valverde, Alfonso (Vall d'Hebron Institut d'Oncologia)
Bazzocco, Sarah (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García-Valverde, Alfonso (Vall d'Hebron Institut d'Oncologia)
Macaya, Irati (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García-Valverde, Alfonso (Vall d'Hebron Institut d'Oncologia)
Arribas, Joaquín V (Universitat Autònoma de Barcelona)
Serrano, César (Hospital Universitari Vall d'Hebron)
Sayós, Joan (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Arango, Diego (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martin, Margarita (Institut d'Investigacions Biomèdiques August Pi i Sunyer)

Date: 2018
Abstract: Gastrointestinal stromal tumors (s) represent about 80% of the mesenchymal neoplasms of the gastrointestinal tract. Most s contain oncogenic (85%) or (5%) receptors. The kinase inhibitor imatinib mesylate is the preferential treatment for these tumors; however, the development of drug resistance has highlighted the need for novel therapeutic strategies. Recently, we reported that the adaptor molecule 3 Binding Protein 2 (32) regulates expression and signaling in human mast cells. Our current study shows that 32 is expressed in primary tumors and cell lines from patients and that 32 silencing leads to a downregulation of oncogenic and expression and an increase in apoptosis in imatinib-sensitive and imatinib-resistant cells. The microphthalmia-associated transcription factor (), involved in expression in mast cells and melanocytes, is expressed in s. Interestingly, is reduced after 32 silencing. Importantly, reconstitution of both 32 and restores cell viability. Furthermore, 32 silencing significantly reduces cell migration and tumor growth of imatinib-sensitive and imatinib-resistant cells in vivo. Altogether, 32 regulates and expression and cell viability, indicating a role as a potential target in imatinib-sensitive and imatinib-resistant s.
Grants: Instituto de Salud Carlos III PI12-00332
Instituto de Salud Carlos III PI16-01371
Ministerio de Economía y Competitividad SAF2015-68124-R
Ministerio de Economía y Competitividad PI12-0310
Ministerio de Economía y Competitividad PI12-01095
Ministerio de Economía y Competitividad PI16-00540
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Subject: Apoptosis ; Gastrointestinal stromal tumors ; SH3BP2
Published in: Molecular Oncology, Vol. 12 (june 2018) , p. 1383-1397, ISSN 1878-0261

DOI: 10.1002/1878-0261.12332
PMID: 29885053


15 p, 1.9 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles

 Record created 2020-07-13, last modified 2023-11-21



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