title: A gene signature distinguishing CD133hi from CD133- colorectal cancer cells: essential role for EGR1 and downstream factors.
abstract: OBJECTIVE
  In colorectal cancer (CRC), CD133 expression is an independent prognostic marker associated with adverse clinical outcome. The CD133 epitope AC133 allowed isolating stem cells from normal and cancerous tissues, although its use in colon was questioned. We aimed to identify differences between AC133 and AC133 cells.
  
  
  METHODS
  We analysed the gene expression profiles of EpCAM/CEA/AC133 and EpCAM/CEA/AC133 cells from primary CRC and liver metastasis tissues (n = 5). Immunohistochemistry confirmed these results in a validation set.
  
  
  RESULTS
  We identified 68 genes differentially expressed between both populations, including genes of notorious importance in CRC pathogenesis, and several candidates not previously shown to play a major role in CRC. Notably, EGR1 belonged to the most highly expressed genes in AC133 cells. In the validation set, the presence of EGR1 and CD133 correlated (r = 0.625). Since EGR1 regulates Wnt through up-regulation of TCF4, which induces stem cell marker LGR5, the potential association between LGR5, EGR1 and CD133 was investigated. The presence of LGR5 correlated with the presence of EGR1 and CD133. Strong signals for LGR5 were detected throughout tumour invasion fronts.
  
  
  CONCLUSIONS
  The study suggests a connection between CD133 and EGR1 and emphasises the importance of the EGR1/TCF4/CD133/LGR5 network in CRC.
authors: Division of Molecular Genetics, German Cancer Research Center, University of Heidelberg, Heidelberg, Germany. aurelie.ernst@ki.se
authors: Aurélie
authors: A
authors: Ernst
authors: Maximilian
authors: M
authors: Aigner
authors: Susumu
authors: S
authors: Nakata
authors: Felix
authors: F
authors: Engel
authors: Magdalena
authors: M
authors: Schlotter
authors: Matthias
authors: M
authors: Kloor
authors: Karsten
authors: K
authors: Brand
authors: Steffen
authors: S
authors: Schmitt
authors: Gunnar
authors: G
authors: Steinert
authors: Nuh
authors: N
authors: Rahbari
authors: Moritz
authors: M
authors: Koch
authors: Bernhard
authors: B
authors: Radlwimmer
authors: Jürgen
authors: J
authors: Weitz
authors: Peter
authors: P
authors: Lichter
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051766:Early Growth Response Protein 1 / Q000235:genetics*; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D053842:Microsatellite Instability; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D000939:Epitopes; D006023:Glycoproteins; C116884:LGR5 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D043562:Receptors, G-Protein-Coupled