title: IGF/STAT3/NANOG/Slug Signaling Axis Simultaneously Controls Epithelial-Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer.
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.
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Chao
authors: C
authors: Yao
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Li
authors: L
authors: Su
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Juanjuan
authors: J
authors: Shan
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Chuanlin
authors: C
authors: Zhu
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Limei
authors: L
authors: Liu
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Chungang
authors: C
authors: Liu
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Yanmin
authors: Y
authors: Xu
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Zhi
authors: Z
authors: Yang
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Xiuwu
authors: X
authors: Bian
authors: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors: Jimin
authors: J
authors: Shao
authors: Department of Pathology, Soochow University School of Medicine, Suzhou, China.
authors: Jianming
authors: J
authors: Li
authors: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors: Maode
authors: M
authors: Lai
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Junjie
authors: J
authors: Shen
authors: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Cheng
authors: C
authors: Qian
mesh_terms: D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D000071317:Nanog Homeobox Protein / Q000096:biosynthesis* / Q000235:genetics; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000096:biosynthesis* / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D000071250:Snail Family Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C000597236:IGF1R protein, human; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D017451:Receptors, Somatomedin; C000604407:SNAI1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071250:Snail Family Transcription Factors; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: Cancer stem cells; EMT; Insulin-like growth factors; Self-renewal; Signal transduction; Stem cell-microenvironment interactions