Oncotarget

Research Papers:

Overexpression of colorectal cancer oncogene CHRDL2 predicts a poor prognosis

Jian Sun, Xuan Liu, Hong Gao, Long Zhang, Qing Ji, Ziyuan Wang, Lihong Zhou2, Yan Wang, Hua Sui, Zhongze Fan and Qi Li _

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Oncotarget. 2017; 8:11489-11506. https://doi.org/10.18632/oncotarget.14039

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Abstract

Jian Sun1,*, Xuan Liu2,*, Hong Gao1, Long Zhang1, Qing Ji2, Ziyuan Wang1, Lihong Zhou2, Yan Wang3, Hua Sui2, Zhongze Fan1, Qi Li2

1Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China

2Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

3Cancer Institute of Traditional Chinese Medicine & Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

*These authors have contributed equally to this work

Correspondence to:

Qi Li, email: [email protected]

Keywords: colorectal cancer, BMP, CHRDL2, proliferation, apoptosis

Received: July 06, 2016     Accepted: November 07, 2016     Published: December 20, 2016

ABSTRACT

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.


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