MACC1 regulates PDL1 expression and tumor immunity through the c-Met/AKT/mTOR pathway in gastric cancer cells.
Cancer Med
; 8(16): 7044-7054, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31557409
ABSTRACT
BACKGROUND:
Immunotherapy and its mechanisms are being studied in a wide variety of cancers. Programmed cell death ligand 1 (PDL1) is associated with immune evasion in numerous tumor types. Here, we aimed to assess the relationship between metastasis associated in colon cancer-1 (MACC1) and PDL1 and examine their effects on gastric cancer (GC) tumor immunity.METHODS:
The expression of MACC1, c-Met, and PDL1 in human GC tissues was first assessed using quantitative RT-PCR (qRT-PCR) and immunohistochemistry. We then focused on the relationships among MACC1, c-Met, and PDL1 using RT-PCR and western blotting after cell transfection and inhibitor treatment in vitro and on the identification of their roles in immune killing in vitro and in vivo.RESULTS:
We found that expression of MACC1, c-Met, and PDL1 was upregulated in human GC tissues, and there was a positive correlation between the expression levels. In addition, we found that ectopic expression of MACC1 (silencing and overexpression by transfection) resulted in corresponding changes in c-Met and PDL1 expression levels, and c-Met/AKT/mTOR pathway inhibitors (SU11274, MK2206, and rapamycin) blocked the regulation of PDL1 expression by MACC1. Furthermore, silencing of MACC1 led to an increase in antitumor and immune killing in vitro and in vivo, and overexpression of MACC1 resulted in a decrease in tumor immunity in vitro and in vivo.CONCLUSIONS:
From these data, we infer that MACC1 regulates PDL1 expression and tumor immunity through the c-Met/AKT/mTOR pathway in GC cells and suggest that MACC1 may be a therapeutic target for GC immunotherapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Transativadores
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Proteínas Proto-Oncogênicas c-met
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Proteínas Proto-Oncogênicas c-akt
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Serina-Treonina Quinases TOR
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Antígeno B7-H1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Med
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China