Exosomes transmit T790M mutation-induced resistance in EGFR-mutant NSCLC by activating PI3K/AKT signalling pathway.
J Cell Mol Med
; 24(2): 1529-1540, 2020 01.
Article
en En
| MEDLINE
| ID: mdl-31894895
ABSTRACT
Emerging evidence has shown that exosomes derived from drug-resistant tumour cells are able to horizontally transmit drug-resistant phenotype to sensitive cells. However, whether exosomes shed by EGFR T790M-mutant-resistant NSCLC cells could transfer drug resistance to sensitive cells has not been investigated. We isolated exosomes from the conditioned medium (CM) of T790M-mutant NSCLC cell line H1975 and sensitive cell line PC9. The role and mechanism of exosomes in regulating gefitinib resistance was investigated both in vitro and in vivo. Exosome-derived miRNA expression profiles from PC9 and H1975 were analysed by small RNA sequencing and confirmed by qRT-PCR. We found that exosomes shed by H1975 could transfer gefitinib resistance to PC9 both in vitro and in vivo through activating PI3K/AKT signalling pathway. Small RNA sequencing and RT-PCR confirmed that miR-3648 and miR-522-3p were the two most differentially expressed miRNAs and functional study showed that up-regulation of miR-522-3p could induce gefitinib resistance in PC9 cell. The findings of our study reveal an important mechanism of acquired resistance to EGFR-TKIs in NSCLC.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
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Resistencia a Antineoplásicos
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Fosfatidilinositol 3-Quinasas
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Proteínas Proto-Oncogénicas c-akt
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Exosomas
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Receptores ErbB
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Neoplasias Pulmonares
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Mutación
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Cell Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2020
Tipo del documento:
Article
País de afiliación:
China