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Hypermethylation of the CHRDL1 promoter induces proliferation and metastasis by activating Akt and Erk in gastric cancer

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机构: [1]Zhejiang Prov Peoples Hosp, Dept Hepatobiliary Pancreat Surg, Hangzhou 310014, Zhejiang, Peoples R China; [2]Capital Med Univ, Bejing Anzhen Hosp, Dept Gen Surg, Beijing 100000, Peoples R China; [3]Hunan Prov Peoples Hosp, Dept Intervent Therapy & Vasc Surg, Changsha, Hunan, Peoples R China; [4]Genetron Hlth Beijing Technol Co Ltd, Beijing 100000, Peoples R China
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关键词: CHRDL1 EMT gastric cancer methylation Wnt

摘要:
CHRDL1 (Chordin-like 1) is a secreted protein that acts as an antagonist of bone morphogenetic protein (BMP). BMP plays a role as an activator of BMP receptor II (BMPR II), which mediates extracellular to intracellular signal transmission and is involved in carcinogenesis and metastasis. Herein, we report that CHRDL1 expression was significantly down-regulated in gastric cancer tissues and associated with poor survival. Clinic-pathological parameters demonstrated a close relationship between low CHRDL1 expression and metastasis. In vitro, CHRDL1 knockdown promoted tumor cell proliferation and migration through BMPR II by activating Akt, Erk and beta-catenin. Furthermore, we observed the hypermethylation of the CHRDL1 promoter in gastric cancer, which induced low expression of CHRDL1 and decreased its secretion to the supernatant. Finally, in vivo experiments confirmed that CHRDL1 acted as a tumor suppressor gene in suppressing tumor growth and metastasis.

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出版当年[2016]版:
大类 | 1 区 医学
小类 | 2 区 细胞生物学 2 区 肿瘤学
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Q1 CELL BIOLOGY Q1 ONCOLOGY
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第一作者机构: [1]Zhejiang Prov Peoples Hosp, Dept Hepatobiliary Pancreat Surg, Hangzhou 310014, Zhejiang, Peoples R China;
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通讯机构: [1]Zhejiang Prov Peoples Hosp, Dept Hepatobiliary Pancreat Surg, Hangzhou 310014, Zhejiang, Peoples R China;
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