GDF15 promotes EMT and metastasis in colorectal cancer

Abstract

// Chen Li 1, 4, * , Jingyu Wang 1, 2, 5, * , Jianlu Kong 1, 4 , Jinlong Tang 1, 3 , Yihua Wu 1 , Enping Xu 1, 4 , Honghe Zhang 1, 4 , Maode Lai 1, 4 1 Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, PR China 2 Department of Pathology, the First Hospital of Jiaxing, Zhejiang, PR China 3 Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, PR China 4 Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China 5 Key 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: honghezhang@zju.edu.cn Maode Lai, e-mail: lmp@zju.edu.cn Keywords: GDF15, EMT, metastasis, colorectal cancer Received: July 21, 2015      Accepted: October 15, 2015      Published: October 22, 2015 ABSTRACT 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.