Oncotarget

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This article has been corrected. Correction in: Oncotarget. 2017; 8:48526.

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

Yao-fei Pei, Ya-jing Zhang, Yao Lei, Ding-wei Wu, Tong-hui Ma and Xi-qiang Liu _

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Oncotarget. 2017; 8:23155-23166. https://doi.org/10.18632/oncotarget.15513

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Abstract

Yao-fei Pei1,*, Ya-jing Zhang2,*, Yao Lei3, Ding-wei Wu1, Tong-hui Ma4, Xi-qiang Liu1

1Department of Hepatobiliary-Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province 310014, PR China

2Department of General Surgery, Bejing Anzhen Hospital, Capital Medical University, Beijing 100000, PR China

3Department of Interventional Therapy and Vascular Surgery, Hunan Provincial People’s Hospital, Changsha, Hunan Province 410005, PR China

4Genetron Health (Beijing) Technology, Co. Ltd., Changping, Beijing 100000, PR China

*These authors contributed equally to this work

Correspondence to:

Xi-qiang Liu, email: [email protected]

Keywords: CHRDL1, EMT, gastric cancer, methylation, Wnt

Received: December 08, 2016     Accepted: February 07, 2017     Published: February 19, 2017

ABSTRACT

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 β-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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