Inhibition of stromal-interacting molecule 1-mediated store-operated Ca2+ entry as a novel strategy for the treatment of acquired imatinib-resistant gastrointestinal stromal tumors.
Cancer Sci
; 109(9): 2792-2800, 2018 Sep.
Article
en En
| MEDLINE
| ID: mdl-29957833
ABSTRACT
Imatinib has revolutionized the treatment of gastrointestinal stromal tumors (GIST); however, primary and secondary resistance to imatinib is still a major cause of treatment failure. Multiple mechanisms are involved in this progression. In the present study, we reported a novel mechanism for the acquired resistance to imatinib, which was induced by enhanced Ca2+ influx via stromal-interacting molecule 1 (STIM1)-mediated store-operated Ca2+ entry (SOCE). We found that the STIM1 expression level was related to the acquired resistance to imatinib in our studied cohort. The function of STIM1 in imatinib-resistant GIST cells was also confirmed both in vivo and in vitro. The results showed that STIM1 overexpression contributed to SOCE and drug response in imatinib-sensitive GIST cells. Blockage of SOCE by STIM1 knockdown suppressed the proliferation of imatinib-resistant GIST cell lines and xenografts. In addition, STIM1-mediated SOCE exerted an antiapoptotic effect via the MEK/ERK pathway. The results from this study provide a basis for further research into potential novel therapeutic strategies in acquired imatinib-resistant GIST.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcio
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Tumores del Estroma Gastrointestinal
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Mesilato de Imatinib
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Molécula de Interacción Estromal 1
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Neoplasias Gastrointestinales
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Proteínas de Neoplasias
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Antineoplásicos
Límite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Cancer Sci
Año:
2018
Tipo del documento:
Article
País de afiliación:
China