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Overexpression of colorectal cancer oncogene CHRDL2 predicts a poor prognosis

2016; Impact Journals LLC; Volume: 8; Issue: 7 Linguagem: Inglês

10.18632/oncotarget.14039

1949-2553

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

Cancer, Lipids, and Metabolism

// Jian Sun 1, * , Xuan Liu 2, * , Hong Gao 1 , Long Zhang 1 , Qing Ji 2 , Ziyuan Wang 1 , Lihong Zhou 2 , Yan Wang 3 , Hua Sui 2 , Zhongze Fan 1 , Qi Li 2 1 Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China 2 Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China 3 Cancer 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: Lzwf@hotmail.com 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.