Overexpression of colorectal cancer oncogene CHRDL2 predicts a poor prognosis

被引:10
|
作者
Sun, Jian [1 ,2 ]
Liu, Xuan [3 ]
Gao, Hong [1 ,2 ]
Zhang, Long [1 ,2 ]
Ji, Qing [3 ]
Wang, Ziyuan [1 ,2 ]
Zhou, Lihong [3 ]
Wang, Yan [4 ,5 ]
Sui, Hua [3 ]
Fan, Zhongze [1 ,2 ]
Li, Qi [3 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Intervent Canc Inst Integrat Med, Shanghai 200062, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Putuo Hosp, Shanghai 200062, Peoples R China
[3] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Med Oncol, Shanghai 201203, Peoples R China
[4] Shanghai Univ Tradit Chinese Med, Canc Inst Tradit Chinese Med, Shanghai 200032, Peoples R China
[5] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
colorectal cancer; BMP; CHRDL2; proliferation; apoptosis; BONE MORPHOGENETIC PROTEIN-2; RECEPTOR RESTORATION; EXPRESSION PATTERNS; CELL-GROWTH; STEM-CELLS; ACTIVIN; APOPTOSIS; PATHWAY; ANTAGONIST; ACTIVATION;
D O I
10.18632/oncotarget.14039
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Bone morphogenetic proteins (BMPs) both promote and suppress tumorigenesis, and multiple BMP antagonists reportedly contribute to cancer progression. In this study, we demonstrated that the BMP antagonist Chordin-like 2 (CHRDL2) is upregulated in colorectal cancer (CRC) tissues, and that CHRDL2 levels correlate with clinical features of CRC patients, including tumor size, TNM staging, and tumor differentiation. In addition, survival rate and Cox proportional hazards model analyses showed that high CHRDL2 levels correlate with a poor prognosis in CRC. Moreover, CHRDL2 promoted CRC cell proliferation in vitro and in vivo, perhaps through up-regulation of Cyclin D1 and down-regulation of P21. Co-immunoprecipitation assays showed that CHRDL2 bound to BMPs, which inhibited p-Smad1/5, thereby promoting CRC cell proliferation and inhibiting apoptosis. These results suggest CHRDL2 could serve as a biomarker of poor prognosis in CRC, and provide evidence that CHRDL2 acts as an oncogene in human CRC, making it a novel potential therapeutic target.
引用
收藏
页码:11489 / 11506
页数:18
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