Upregulated NTF4 in colorectal cancer promotes tumor development via regulating autophagy.
Int J Oncol
; 56(6): 1442-1454, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32236587
ABSTRACT
Autophagy plays a key role in colorectal cancer (CRC) development and reduces the sensitivity of CRC cells to treatment. The present study reported a novel tumorsuppressive role for autophagy, which was demonstrated to be regulated through the novel oncogene neurotrophin4 (NTF4). NTF4 was significantly overexpressed in tumor tissue compared with nontumor mucosa, and the upregulation of NTF4 in CRC was associated with poor overall survival and advanced TNM stage. The genetic knockdown of NTF4 using short hairpin RNA in CRC cells prevented epithelialtomesenchymal transition and activated autophagy; this was regulated through the interaction between autophagyassociated gene 5 (Atg5) and the mitogenactivated protein kinase pathway. In addition, the knockdown of NTF4 inhibited cell invasion, migration, proliferation and colony formation, and promoted cell cycle arrest. Treatment of the cells with the autophagy inhibitor chloroquine (CQ) rescued these functions and promoted cell invasion, migration, proliferation and colony formation. Finally, the knockdown of NTF4 inhibited the growth of subcutaneous xenografts in Balb/cnu mice. In conclusion, these findings suggested that NTF4 may be a diagnostic marker associated with the overall survival and progression of patients with CRC. NTF4 was found to promote tumorigenesis and CRC development through autophagy regulation.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Regulação para Cima
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Fatores de Crescimento Neural
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article