title: Notch1 signaling regulates the epithelial-mesenchymal transition and invasion of breast cancer in a Slug-dependent manner.
abstract: BACKGROUND
  The epithelial-mesenchymal transition (EMT) is crucial for the invasion and metastasis of breast cancer. However, how Notch signaling regulates the EMT process and invasion in breast cancer remains largely unknown.
  
  
  METHODS
  The impact of Notch1 silencing by specific shRNAs on the EMT and invasion of human breast cancer MCF-7 and MDA-MB-231 cells as well as xenografts was tested by western blot, real-time polymerase chain reaction (RT-PCR), immunofluorescence, transwell, and immunohistochemistry assays. The effect of Slug silencing or upregulation on the EMT and invasion of breast cancer cells was analyzed, and the effect of Notch1 signaling on Slug expression was determined by the luciferase reporter assay.
  
  
  RESULTS
  The Notch1 intracellular domain (N1ICD) and Jagged1 were expressed in breast cancer cells. Notch1 silencing reversed the spontaneous EMT process and inhibited the migration and invasion of breast cancer cells and the growth of xenograft breast cancers. The expression of N1ICD was upregulated significantly by Jagged1-mediated Notch signaling activation. Moreover, Jagged1-mediated Notch signaling promoted the EMT process, migration, and invasion of breast cancer cells, which were abrogated by Notch silencing. Furthermore, the N1ICD positively regulated the Slug expression by inducing Slug promoter activation. Importantly, the knockdown of Slug weakened the invasion ability of breast cancer cells and reversed the Jagged1-induced EMT process with significantly decreased expression of vimentin and increased expression of E-cadherin. In addition, Slug overexpression restored the Notch1 knockdown-suppressed EMT process.
  
  
  CONCLUSIONS
  Our novel data indicate that Notch signaling positively regulates the EMT, invasion, and growth of breast cancer cells by inducing Slug expression. The Notch1-Slug signaling axis may represent a potential therapeutic target for breast cancer therapy.
authors: The Department of Oncology, the First Hospital Affiliated to the School of Medicine, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China. shaoshan@stu.xjtu.edu.cn.
authors: Shan
authors: S
authors: Shao
authors: The Department of Oncology, the First Hospital Affiliated to the School of Medicine, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China. zxa1112@163.com.
authors: Xiaoai
authors: X
authors: Zhao
authors: The Department of Oncology, the First Hospital Affiliated to the School of Medicine, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China. zhxj824@163.com.
authors: Xiaojin
authors: X
authors: Zhang
authors: The Department of Oncology, the First Hospital Affiliated to the School of Medicine, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China. luominna@stu.xjtu.edu.cn.
authors: Minna
authors: M
authors: Luo
authors: The Department of Oncology, the First Hospital Affiliated to the School of Medicine, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China. zuoxiao1985@163.com.
authors: Xiaoxiao
authors: X
authors: Zuo
authors: The Department of Oncology, the First Hospital Affiliated to the School of Medicine, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China. hsk511469993@163.com.
authors: Shangke
authors: S
authors: Huang
authors: The Department of Oncology, the First Hospital Affiliated to the School of Medicine, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China. wangying_0821@163.com.
authors: Ying
authors: Y
authors: Wang
authors: The Department of Forensic Medicine, Medical School, Xi'an Jiaotong University, 76 West Yanta Road, Xi'an, 710061, Shaanxi Province, China. gushanzhi@mail.xjtu.edu.cn.
authors: Shanzhi
authors: S
authors: Gu
authors: The Department of Oncology, the First Hospital Affiliated to the School of Medicine, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, China. zhaoxinhanprof@163.com.
authors: Xinhan
authors: X
authors: Zhao
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051881:Receptor, Notch1; C000604407:SNAI1 protein, human; D000072099:Serrate-Jagged Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
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