EB virus-induced ATR activation accelerates nasopharyngeal carcinoma growth via M2-type macrophages polarization.
Cell Death Dis
; 11(9): 742, 2020 09 11.
Article
en En
| MEDLINE
| ID: mdl-32917854
ABSTRACT
Chronic inflammation induced by persistent viruses infection plays an essential role in tumor progression, which influenced on the interaction between the tumor cells and the tumor microenvironment. Our earlier study showed that ATR, a key kinase participant in single-stranded DNA damage response (DDR), was obviously activated by Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC). However, how EBV-induced ATR activation promotes NPC by influencing inflammatory microenvironment, such as tumor-associated macrophages (TAMs), remains elusive. In this study, we showed that EBV could promote the expression of p-ATR and M2-type TAMs transformation in clinical NPC specimens. The expression of p-ATR and M2-type TAMs were closely correlated each other and involved in TNM stage, lymph node metastasis and poor prognosis of the patients. In addition, the expression levels of CD68+CD206+, Arg1, VEGF, and CCL22 were increased in EB+ CNE1 cells, and decreased when ATR was inhibited. In the nude mice, EBV-induced ATR activation promoted subcutaneous transplanted tumor growth, higher expression of Ki67 and lung metastasis via M2-type TAMs recruitment. Experimental data also showed that the polarization of M2, the declined tumor necrosis factor-α (TNF-α) and increased transforming growth factor-ß (TGF-ß) were associated with ATR. Meanwhile, ATR activation could promote PPAR-δ and inhibited c-Jun and p-JNK expression, then downregulate JNK pathway. Collectively, our current study demonstrated the EBV infection could activate the ATR pathway to accelerate the transition of TAMs to M2, suggesting ATR knockdown could be a potential effective treatment strategy for EBV-positive NPC.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Infecciones por Virus de Epstein-Barr
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Proteínas de la Ataxia Telangiectasia Mutada
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Carcinoma Nasofaríngeo
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Inmunoterapia
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Activación de Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cell Death Dis
Año:
2020
Tipo del documento:
Article
País de afiliación:
China