Retinoic Acid Receptor α Knockdown Suppresses the Tumorigenicity of Esophageal Carcinoma via Wnt/β-catenin Pathway
| Autor: | Dong-Yan Shen, Qi-Rui Fu, Pan Zhou, Qian-En Chen, Xiao-Yun Zhang, Yu Liu, Xiao-Mei Mao, Jin-Xing Shen, Hua Li, Qing-Xi Chen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Acute promyelocytic leukemia Male Esophageal Neoplasms Physiology Carcinogenesis Cell Survival MMP9 medicine.disease_cause 03 medical and health sciences Gene Knockout Techniques 0302 clinical medicine Downregulation and upregulation Cell Line Tumor medicine Humans Wnt Signaling Pathway Tumor Stem Cell Assay Cell Proliferation Neoplasm Staging Gene knockdown Chemistry Retinoic Acid Receptor alpha Gastroenterology Wnt signaling pathway Middle Aged medicine.disease Immunohistochemistry Gene Expression Regulation Neoplastic Retinoic acid receptor 030104 developmental biology 030220 oncology & carcinogenesis Catenin Cancer research Female |
| Zdroj: | Digestive diseases and sciences. 63(12) |
| ISSN: | 1573-2568 |
| Popis: | 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. To investigate the expression of RARα in EC and its effect in the tumorigenesis of EC. 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/β-catenin pathway through reducing the phosphorylation level of GSK3β 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. Our results demonstrated that RARα knockdown suppressed the tumorigenicity of EC via Wnt/β-catenin pathway. RARα might be a potential molecular target for EC clinical therapy. |
| Databáze: | OpenAIRE |
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