The E2F1/USP11 positive feedback loop promotes hepatocellular carcinoma metastasis and inhibits autophagy by activating ERK/mTOR pathway.
Cancer Lett
; 514: 63-78, 2021 08 28.
Article
em En
| MEDLINE
| ID: mdl-34044068
ABSTRACT
Deubiquitinase ubiquitin-specific protease 11 (USP11), a member of the deubiquitinating family, plays an important but still controversial role in cancer development. Namely, USP11 has been shown to promote the proliferation and metastasis of hepatocellular carcinoma (HCC), but the underlying molecular basis is poorly understood. This study aimed to unravel novel functions of USP11 in HCC, especially those related to autophagy. Here, EdU, migration and colony formation assays, and mouse models showed that USP11 played a crucial role in HCC cell proliferation and metastasis in vitro and in vivo. Results from co-immunoprecipitation and ubiquitination assays demonstrated that USP11 interacted with E2F1 and maintained E2F1 protein stability by removing its ubiquitin. Notably, E2F1 regulated USP11 expression at the transcriptional level. Thus, the E2F1/USP11 formed a positive feedback loop to promote the proliferation and migration of HCC cells. Moreover, E2F1/USP11 inhibited autophagy by regulating ERK/mTOR pathway. In addition, the combination treatment inhibition of USP11 and autophagy enhanced the apoptosis of HCC cells and inhibited the tumor growth in mice more effective than either treatment alone. Taken together, these results indicate that the E2F1/USP11 signal axis promotes HCC proliferation and metastasis and inhibits autophagy, which provides an experimental basis for the treatment of HCC.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Tioléster Hidrolases
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Carcinoma Hepatocelular
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Sistema de Sinalização das MAP Quinases
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Fator de Transcrição E2F1
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Serina-Treonina Quinases TOR
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Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Lett
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China