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Title: The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth
Author: Proaño Pérez, Elisabeth
Serrano Candelas, Eva
García-Valverde, Alfonso
Rosell, Jordi
Gómez Peregrina, David
Navinés Ferrer, Arnau
Guerrero, Mario
Serrano, César
Martín Andorrà, Margarita
Keywords: Factors de transcripció
Càncer gastrointestinal
Transducció de senyal cel·lular
Transcription factors
Gastrointestinal cancer
Cellular signal transduction
Issue Date: 14-Oct-2022
Publisher: Springer Nature
Abstract: Gastrointestinal stromal tumors (GISTs) are the most common neoplasms of mesenchymal origin, and most of them emerge due to the oncogenic activation of KIT or PDGFRA receptors. Despite their relevance in GIST oncogenesis, critical intermediates mediating the KIT/PDGFRA transforming program remain mostly unknown. Previously, we found that the adaptor molecule SH3BP2 was involved in GIST cell survival, likely due to the co-regulation of the expression of KIT and Microphthalmia-associated transcription factor (MITF). Remarkably, MITF reconstitution restored KIT expression levels in SH3BP2 silenced cells and restored cell viability. This study aimed to analyze MITF as a novel driver of KIT transforming program in GIST. Firstly, MITF isoforms were characterized in GIST cell lines and GIST patients' samples. MITF silencing decreases cell viability and increases apoptosis in GIST cell lines irrespective of the type of KIT primary or secondary mutation. Additionally, MITF silencing leads to cell cycle arrest and impaired tumor growth in vivo. Interestingly, MITF silencing also affects ETV1 expression, a linage survival factor in GIST that promotes tumorigenesis and is directly regulated by KIT signaling. Altogether, these results point to MITF as a key target of KIT/PDGFRA oncogenic signaling for GIST survival and tumor growth.
Note: Versió postprint del document publicat a
It is part of: Cancer Gene Therapy, 2022, vol. 30, num.2, p. 245-255
ISSN: 0929-1903
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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