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Title: Silencing of adaptor protein SH3BP2 reduces KIT/PDGFRA receptors expression and impairs gastrointestinal stromal tumors growth.
Author: Serrano Candelas, Eva
Ainsua-Enrich, Erola
Navinés Ferrer, Arnau
Rodrigues, Paulo
García Valverde, Alfonso
Bazzocco, Sarah
Macaya, Irati
Arribas López, Joaquín
Serrano, César
Sayós Ortega, Juan
Arango, Diego
Martín Andorrà, Margarita
Keywords: Apoptosi
Malalties del tracte gastrointestinal
Gastrointestinal system diseases
Issue Date: 9-Jun-2018
Publisher: Elsevier
Abstract: Gastrointestinal stromal tumors (GISTs) represent about 80% of the mesenchymal neoplasms of the gastrointestinal tract. Most GISTs contain oncogenic KIT (85%) or PDGFRA (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 SH3 Binding Protein 2 (SH3BP2) regulates KIT expression and signaling in human mast cells. Our current study shows that SH3BP2 is expressed in primary tumors and cell lines from GIST patients and that SH3BP2 silencing leads to a downregulation of oncogenic KIT and PDGFRA expression and an increase in apoptosis in imatinib-sensitive and imatinib-resistant GIST cells. The microphthalmia-associated transcription factor (MITF), involved in KIT expression in mast cells and melanocytes, is expressed in GISTs. Interestingly, MITF is reduced after SH3BP2 silencing. Importantly, reconstitution of both SH3BP2 and MITF restores cell viability. Furthermore, SH3BP2 silencing significantly reduces cell migration and tumor growth of imatinib-sensitive and imatinib-resistant cells in vivo. Altogether, SH3BP2 regulates KIT and PDGFRA expression and cell viability, indicating a role as a potential target in imatinib-sensitive and imatinib-resistant GISTs.
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It is part of: Molecular Oncology, 2018
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ISSN: 1574-7891
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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