IGF/STAT3/NANOG/Slug Signaling Axis Simultaneously Controls Epithelial‐Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer. (26th February 2016)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Stem cells. Volume 34:Number 4(2016:Apr.)
• Page Start: 820
• Page End: 831
• Publication Date: 2016-02-26
• Subjects: Cancer stem cells -- EMT -- Insulin‐like growth factors -- Self‐renewal -- Stem cell‐microenvironment interactions -- Signal transduction; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2320
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: 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. Stem Cells 2016;34:820–831