Open AccessIGF/STAT3/NANOG/Slug Signaling Axis Simultaneously Controls Epithelial‐Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer
Author(s) -
Yao Chao,
Su Li,
Shan Juanjuan,
Zhu Chuanlin,
Liu Limei,
Liu Chungang,
Xu Yanmin,
Yang Zhi,
Bian Xiuwu,
Shao Jimin,
Li Jianming,
Lai Maode,
Shen Junjie,
Qian Cheng
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2320
Subject(s) - homeobox protein nanog , slug , epithelial–mesenchymal transition , biology , cancer research , cancer stem cell , colorectal cancer , metastasis , signal transduction , twist transcription factor , nanog homeobox protein , rex1 , stat3 , stem cell , cancer , embryonic stem cell , microbiology and biotechnology , induced pluripotent stem cell , genetics , gene
Discovery of epithelial‐mesenchymal transition (EMT) and cancer stem cells (CSCs) are two milestones in people exploring the nature of malignant tumor in recent decades. Although some studies have presented the potential connections between them, the link details, underneath their superficial correlation, are largely unknown. In this study, we identified a small subpopulation of NANOG‐positive colorectal cancer (CRC) cells, and demonstrated that they exhibited characteristics of CSCs and EMT traits simultaneously. Furthermore, we found that NANOG was a core factor in regulating both of EMT and stemness in CRC cells, NANOG modulate EMT and metastasis by binding to Slug promoter and transcriptionally regulate Slug expression. For the first time, we demonstrated that NANOG was regulated by extracellular IGF signaling pathway via STAT3 phosphorylation in CRC. This coincides with that IGF receptor IGF‐1R is often increasing expressed in malignant metastasis colon cancer. Taken together, our data define the crucial functions of IGF/STAT3/NANOG/Slug signaling axis in the progression of CRC by operating EMT and CSCs properties, which make them served as potential therapeutic targets for treatment of CRC. S tem C ells 2016;34:820–831