Paradoxical effects of DNA tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response.
Signal Transduct Target Ther
; 6(1): 408, 2021 11 26.
Article
em En
| MEDLINE
| ID: mdl-34836940
ABSTRACT
Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection is the risk factors for nasopharyngeal carcinoma and cervical carcinoma, respectively. However, clinical analyses demonstrate that EBV or HPV is associated with improved response of patients, although underlying mechanism remains unclear. Here, we reported that the oncoproteins of DNA viruses, such as LMP1 of EBV and E7 of HPV, inhibit PERK activity in cancer cells via the interaction of the viral oncoproteins with PERK through a conserved motif. Inhibition of PERK led to increased level of reactive oxygen species (ROS) that promoted tumor and enhanced the efficacy of chemotherapy in vivo. Consistently, disruption of viral oncoprotein-PERK interactions attenuated tumor growth and chemotherapy in both cancer cells and tumor-bearing mouse models. Our findings uncovered a paradoxical effect of DNA tumor virus oncoproteins on tumors and highlighted that targeting PERK might be an attractive strategy for the treatment of NPC and cervical carcinoma.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Papillomaviridae
/
Neoplasias do Colo do Útero
/
Proteínas Oncogênicas Virais
/
Proteínas da Matriz Viral
/
Neoplasias Nasofaríngeas
/
Herpesvirus Humano 4
/
Infecções por Vírus Epstein-Barr
/
Infecções por Papillomavirus
/
Carcinoma Nasofaríngeo
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Signal Transduct Target Ther
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China