title: Prolyl hydroxylase 3 inhibited the tumorigenecity of gastric cancer cells.
abstract: 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.
authors.affiliation: General Surgery Department, Affiliated Hospital of Jiangsu University, Zhenjiang City, Jiangsu Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.forename: Jianguo
authors.initials: J
authors.lastname: Qu
authors.forename: Shengchun
authors.initials: S
authors.lastname: Dang
authors.forename: Zhengfa
authors.initials: Z
authors.lastname: Mao
authors.forename: Xuqing
authors.initials: X
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Fan
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering / Q000235:genetics; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D051176:beta Catenin; C488894:EGLN3 protein, human; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases
keywords: beta-catenin/TCF; cell growth; gastric cancer; prolyl hydroxylase 3