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. H...

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Published in:Oncotarget Vol. 7; no. 1; p. 860
Main Authors: Li, Chen, Wang, Jingyu, Kong, Jianlu, Tang, Jinlong, Wu, Yihua, Xu, Enping, Zhang, Honghe, Lai, Maode
Format: Journal Article
Language:English
Published: United States 05.01.2016
Subjects:
Animals
Cell Line, Tumor
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Epithelial-Mesenchymal Transition - genetics
Female
Gene Expression Regulation, Neoplastic
Growth Differentiation Factor 15 - blood
Growth Differentiation Factor 15 - genetics
Growth Differentiation Factor 15 - metabolism
HEK293 Cells
HT29 Cells
Humans
Immunoblotting
Immunohistochemistry
Male
Mice, Inbred NOD
Mice, SCID
Middle Aged
Neoplasm Metastasis
Proportional Hazards Models
Receptors, Transforming Growth Factor beta - genetics
Receptors, Transforming Growth Factor beta - metabolism
Reverse Transcriptase Polymerase Chain Reaction - statistics & numerical data
RNA Interference
Smad2 Protein - genetics
Smad2 Protein - metabolism
Smad3 Protein - genetics
Smad3 Protein - metabolism
Survival Analysis
Transplantation, Heterologous
colorectal cancer
GDF15
metastasis
EMT
ISSN:1949-2553, 1949-2553
Online Access:Get more information
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Summary: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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SourceType-Scholarly Journals-1
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ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.6205