title: Evidence of the cross talk between Wnt and Notch signaling pathways in non-small-cell lung cancer (NSCLC): Notch3-siRNA weakens the effect of LiCl on the cell cycle of NSCLC cell lines.
abstract: BACKGROUND
  Aberrant activations of Wnt and Notch signaling pathways are individually reported to be associated with the pathogenesis of non-small-cell lung cancer (NSCLC). However, the data about the cross talk between the two signaling pathways are still limited. To elucidate potential Wnt/Notch cross talk within NSCLC, we examined the impact of Notch3 activity on LiCl-induced cell cycle changes.
  
  
  METHODS
  The lung cancer cell lines were treated with LiCl, a Wnt activator, in the absence or presence of Notch3-siRNA. Cell cycles and the expression of the regulators of cell cycle, c-MYC, p21 and Skp2 (S phase kinase-associated protein 2) were measured after treatment.
  
  
  RESULTS
  The treatment with LiCl increased the percent of cells at S phase and G phase and the expression of c-MYC and Skp2 and decreased the expression of p21. Moreover, the expression of Notch3 and its down-stream genes, HES-1 and HEYL, was up-regulated by LiCl. Notch3-siRNA weakened the effect of LiCl on the cell cycle and resulted in attenuation of the LiCl-induced increment of c-MYC and Skp2 and the LiCl-induced decrement of p21.
  
  
  CONCLUSIONS
  These data suggest that Notch3 activation cooperatively takes part in the LiCl-induced cell cycle changes, at least partially, associated with c-MYC, Skp2 and p21.
authors.affiliation: Center of Laboratory Technology and Experimental Medicine, China Medical University, 110001, Shenyang, People's Republic of China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.forename: Zeshi
authors.initials: Z
authors.lastname: Cui
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Siyang
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Xue
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000502:physiology*; D044786:S-Phase Kinase-Associated Proteins / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C489427:MYC protein, human; C499374:NOTCH3 protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D044786:S-Phase Kinase-Associated Proteins; D051153:Wnt Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride