Research Papers:

GDF15 promotes EMT and metastasis in colorectal cancer

Chen Li, Jingyu Wang, Jianlu Kong, Jinlong Tang, Yihua Wu, Enping Xu, Honghe Zhang _ and Maode Lai

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Oncotarget. 2016; 7:860-872. https://doi.org/10.18632/oncotarget.6205

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Chen Li1,4,*, Jingyu Wang1,2,5,*, Jianlu Kong1,4, Jinlong Tang1,3, Yihua Wu1, Enping Xu1,4, Honghe Zhang1,4, Maode Lai1,4

1Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, PR China

2Department of Pathology, the First Hospital of Jiaxing, Zhejiang, PR China

3Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, PR China

4Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China

5Key Constructing Discipline by Zhejiang Province and Jiaxing City, Zhejiang, PR China

*These authors have contributed equally to this work

Correspondence to:

Honghe Zhang, e-mail: [email protected]

Maode Lai, e-mail: [email protected]

Keywords: GDF15, EMT, metastasis, colorectal cancer

Received: July 21, 2015     Accepted: October 15, 2015     Published: October 22, 2015


Metastasis is the major cause of cancer deaths, and the epithelial–mesenchymal transition (EMT) has been considered to be a fundamental event in cancer metastasis. However, the role of growth differentiation factor 15 (GDF15) in colorectal cancer (CRC) metastasis and EMT remains poorly understood. Here, we showed that GDF15 promoted CRC cell metastasis both in vitro and in vivo. In addition, the EMT process was enhanced by GDF15 through binding to TGF-β receptor to activate Smad2 and Smad3 pathways. Clinical data showed GDF15 level in tumor tissues, and the serum was significantly increased, in which high GDF15 level correlated with a reduced overall survival in CRC. Thus, GDF15 may promote colorectal cancer metastasis through activating EMT. Promisingly, GDF15 could be considered as a novel prognostic marker for CRC in the clinic.

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