title: Study of the interaction among Notch pathway receptors, correlation with stemness, as well as their interaction with CD44, dipeptidyl peptidase-IV, hepatocyte growth factor receptor and the SETMAR transferase, in colon cancer stem cells.
abstract: BACKGROUND
  The Notch signaling pathway is one of the most important pathways during normal development and implicated in self-renewal of adult stem cells and differentiation of progenitor cells. Abnormal expression of Notch receptors has been associated with many epithelial metaplastic and neoplastic lesions. OBJECTIVE-MATERIALS AND METHODS: In this particular study, it was determined the relative gene expression of Notch receptors after knockdown experiments in colon cancer stem cells (CSCs) and the gene expression changes in stemness transcription factors (Oct4, Sox2, Nanog), as well in dipeptidylpeptidase-4, CD44 antigen, Met proto-oncogene and in Metnase transposase.
  
  
  RESULTS
  In control CSCs Notch-2 had the higher expression, followed by Notch-1, Notch-3. Notch-4 demonstrated the lower gene expression among the receptors. The suppression of Notch-1 led to increased expression of Oct4 and Sox2, but in decreased gene expression of cMET, Setmar and CD44. The CD26 expression remained unchanged. The knockdown of Notch-2 led to decreased expression of all transcription factors. Notch-3 down regulation caused increased Oct4 gene expression, but decreased levels for the rest of the genes. Finally, the suppression of Notch-4 had the same effect as in receptor Notch-3.
  
  
  CONCLUSIONS
  The above experimental data suggest the possible interaction between the four different receptors of Notch signaling pathway. The expression of CD26, cMET and N-methyltransferase Setmar was also changed. Finally, the stemness phenotype was changed in a different way each time, according to the receptor that was down regulated. All Notch receptors and particularly Notch-2 seem to play an important role in cancer stem cells.
authors: Research Genetic Cancer Centre Ltd (R.G.C.C. Ltd) , Florina , Greece .
authors: Panagiotis
authors: P
authors: Apostolou
authors: Maria
authors: M
authors: Toloudi
authors: Eleni
authors: E
authors: Ioannou
authors: Eleni
authors: E
authors: Kourtidou
authors: Marina
authors: M
authors: Chatziioannou
authors: Asir
authors: A
authors: Kopic
authors: Dimitrios
authors: D
authors: Komiotis
authors: Christos
authors: C
authors: Kiritsis
authors: Stella
authors: S
authors: Manta
authors: Ioannis
authors: I
authors: Papasotiriou
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D051880:Receptors, Notch / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051880:Receptors, Notch; D011495:Histone-Lysine N-Methyltransferase; C510450:SETMAR protein, human; D019859:Proto-Oncogene Proteins c-met; D018819:Dipeptidyl Peptidase 4