IGF/STAT3/NANOG/Slug Signaling Axis Simultaneously Controls Epithelial-Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer
IGF/STAT3/NANOG/Slug Signaling Axis Simultaneously Controls Epithelial-Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer
复制标题
IGF/STAT3/NANOG/Slug 信号轴同时控制结直肠癌的上皮-间质转化和干性维持
DOI：
10.1002/stem.2320
复制
发表时间：
2016-04-01
期刊：
影响因子：
5.2
通讯作者：
Qian, Cheng
中科院分区：
文献类型：
--
作者：
Yao, Chao;Su, Li;Qian, Cheng
上皮-间充质转化(EMT)和肿瘤干细胞(CSCs)的发现是近几十年来人们探索恶性肿瘤本质的两个里程碑。尽管一些研究已经提出了它们之间的潜在联系，但在它们表面的关联之下，联系的细节在很大程度上是未知的。在这项研究中，我们鉴定了一小部分NANOG阳性的结直肠癌(CRC)细胞，并证明它们同时具有CSCs和EMT的特征。此外，我们还发现NANOG是调节大肠癌细胞EMT和干性的核心因素，NANOG通过与Slug启动子结合并在转录水平上调节Slug的表达来调节EMT和转移。我们首次证明NANOG在结直肠癌中通过STAT3的磷酸化受细胞外IGF信号通路的调节。这与IGF受体IGF-1R在恶性转移性结肠癌中表达增加不谋而合。综上所述，我们的数据定义了IGF/STAT3/NANOG/SLUG信号轴通过调节EMT和CSCs的特性在结直肠癌进展中的关键作用，使它们成为治疗结直肠癌的潜在靶点。干细胞2016；34：820-831
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 Cells2016;34:820-831