GDF15 promotes EMT and metastasis in colorectal cancer.
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.
Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, PR China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China.
Chen
C
Li
Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, PR China.|Department of Pathology, the First Hospital of Jiaxing, Zhejiang, PR China.|Key Constructing Discipline by Zhejiang Province and Jiaxing City, Zhejiang, PR China.
Jingyu
J
Wang
Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, PR China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China.
Jianlu
J
Kong
Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, PR China.|Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, PR China.
Jinlong
J
Tang
Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, PR China.
Yihua
Y
Wu
Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, PR China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China.
Enping
E
Xu
Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, PR China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China.
Honghe
H
Zhang
Department of Pathology, School of Medicine, Zhejiang University, Zhejiang, PR China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China.
Maode
M
Lai
D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055436:Growth Differentiation Factor 15 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D034622:RNA Interference; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D014183:Transplantation, Heterologous
C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; D051900:Smad3 Protein
EMT; GDF15; colorectal cancer; metastasis