title: Notch1 controls cell invasion and metastasis in small cell lung carcinoma cell lines.
abstract: BACKGROUND
  Notch signaling plays a key role in a wide variety of human neoplasms, and it can be either oncogenic or anti-proliferative. Moreover, Notch function in regulating cancer is unpredictable, and its outcome is strictly context-dependent.
  
  
  OBJECTIVE
  To study the role of Notch1 signaling in human small cell lung carcinoma (SCLC) and its effect on cell invasion and metastasis.
  
  
  METHODS
  We used small interfering RNA (siRNA) technology, to down-regulate the expression of Notch1 in H69AR and SBC3 SCLC cells. On the other hand, we up-regulated Notch1 in H69 and H1688 SCLC cells through transfection with venus Notch1 intracellular domain (v.NICD) plasmid. In addition, H69 cells with v.NICD were xenotransplanted into immune-compromised Rag2(-/-) Jak3(-/-) mice, for analysis of ex vivo tumor epithelial mesenchymal transition (EMT) phenotype and for detection of metastatic cancer cells in the lung tissues. Moreover, we examined the metastatic ability for H69AR and SBC3 cells transfected with siRNA against Notch1, compared to their subsequent controls, by use of tail vein xenograft mouse models.
  
  
  RESULTS
  Notch1 controls cell adhesion and EMT. Overexpression of Notch1 in SCLC switched off EMT, cell motility and cell metastatic potential.
  
  
  CONCLUSIONS
  Our results demonstrate that activation of Notch1 signaling pathway may represent a new strategy for treating human SCLC.
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan; Department of Pathology, Faculty of Medicine, Suez Canal University, Egypt.
authors.forename: Wael Abdo
authors.initials: WA
authors.lastname: Hassan
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University, Graduate School of Medical Sciences, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Niimori-Kita
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan. Electronic address: takaito@kumamoto-u.ac.jp.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1
keywords: Cell metastatic potential; Cell motility; Epithelial mesenchymal transition (EMT); Notch1 signaling; Small cell lung carcinoma (SCLC); Tail vein xenograft mouse model