Retinoic Acid Receptor α Knockdown Suppresses the Tumorigenicity of Esophageal Carcinoma via Wnt/ß-catenin Pathway.
Dig Dis Sci
; 63(12): 3348-3358, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30155836
ABSTRACT
BACKGROUND:
Aberrant expression of retinoic acid receptor α (RARα) was correlated with diverse carcinomas such as acute promyelocytic leukemia and colorectal carcinoma. Nevertheless, the function and mechanism of RARα in esophageal carcinoma (EC) remain unclear.AIM:
To investigate the expression of RARα in EC and its effect in the tumorigenesis of EC. METHODS ANDRESULTS:
In immunohistochemistry study, RARα was overexpressed in human EC tissues, and its overexpression was closely related to the pathological differentiation, lymph node metastasis, and clinical stages in EC patients. Functionally, RARα knockdown suppressed the proliferation and metastasis of EC cells through downregulating the expression of PCNA, Ki67, MMP7, and MMP9, as well as enhanced drug susceptibility of EC cells to 5-fluorouracil and cisplatin. Mechanistically, RARα knockdown inhibited the activity of Wnt/ß-catenin pathway through reducing the phosphorylation level of GSK3ß at Ser-9 and inducing phosphorylation level at Tyr-216, which resulted in downregulation of its downstream targets such as MMP7, MMP9, and P-gP.CONCLUSIONS:
Our results demonstrated that RARα knockdown suppressed the tumorigenicity of EC via Wnt/ß-catenin pathway. RARα might be a potential molecular target for EC clinical therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Esofágicas
/
Regulação Neoplásica da Expressão Gênica
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Via de Sinalização Wnt
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Receptor alfa de Ácido Retinoico
Limite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Dig Dis Sci
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China