Prolyl hydroxylase 3 inhibited the tumorigenecity of gastric cancer cells

Gastric cancer is one of the most common malignancies and the second leading cause of cancer‐related death in the world, and it is very urgent to develop novel therapeutic strategies. Although HIF‐1α is the most highly characterized target of prolyl hydroxylase 3 (PHD3), PHD3 has been shown to regul...

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Bibliographic Details
Published in:Molecular carcinogenesis 2014-09, Vol.53 (9), p.736-743
Main Authors: Cui, Lei, Qu, Jianguo, Dang, Shengchun, Mao, Zhengfa, Wang, Xuqing, Fan, Xin, Sun, Kang, Zhang, Jianxin
Format: Article
Language:English
Subjects:
Animals
Apoptosis
beta Catenin - metabolism
beta-catenin/TCF
Blotting, Western
Case-Control Studies
cell growth
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Cell Transformation, Neoplastic - pathology
Chemotherapy
Female
Gastric cancer
Humans
Hypoxia-Inducible Factor-Proline Dioxygenases - antagonists & inhibitors
Hypoxia-Inducible Factor-Proline Dioxygenases - genetics
Hypoxia-Inducible Factor-Proline Dioxygenases - metabolism
Immunoenzyme Techniques
Immunoprecipitation
Male
Mice
Mice, Nude
Neoplasm Metastasis
prolyl hydroxylase 3
RNA, Small Interfering - genetics
Stomach - metabolism
Stomach - pathology
Stomach Neoplasms - enzymology
Stomach Neoplasms - pathology
Stomach Neoplasms - prevention & control
Tumor Cells, Cultured
Tumorigenesis
Xenograft Model Antitumor Assays
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Summary:Gastric cancer is one of the most common malignancies and the second leading cause of cancer‐related death in the world, and it is very urgent to develop novel therapeutic strategies. Although HIF‐1α is the most highly characterized target of prolyl hydroxylase 3 (PHD3), PHD3 has been shown to regulate several signal pathways independent of HIF‐1α. Here, we found that the expression of PHD3 was decreased in the clinical gastric cancer samples and reversely correlated with tumor size and tumor stage. Over‐expression of PHD3 in the gastric cancer cells significantly inhibited cell growth in vitro and in vivo, while knockdown the expression of PHD3 promoted the tumorigenecity of gastric cancer cells. Mechanistically, it showed that PHD3 downregulated the expression of beta‐catenin and inhibited beta‐catenin/T‐cell factor (TCF) signaling. Taken together, our findings demonstrate that PHD3 inhibits gastric cancer by suppressing the beta‐catenin/TCF signaling and PHD3 might be an important therapeutic target in gastric cancer. Copyright © 2013 Wiley Periodicals, Inc.
ISSN:0899-1987
1098-2744
DOI:10.1002/mc.22025