title: DEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer.
abstract: BACKGROUND
  DEK is a transcription factor involved in stabilization of heterochromatin and cruciform structures. It plays an important role in development and progression of different types of cancer. This study aims to analyze the role of DEK in metastatic colorectal cancer.
  
  
  METHODS
  Baseline DEK expression was firstly quantified in 9 colorectal cell lines and normal mucosa by WB. SiRNA-mediated DEK inhibition was carried out for transient DEK silencing in DLD1 and SW620 to dissect its role in colorectal cancer aggressiveness. Irinotecan response assays were performed with SN38 over 24 hours and apoptosis was quantified by flow cytometry. Ex-vivo assay was carried out with 3 fresh tumour tissues taken from surgical resection and treated with SN38 for 24 hours. DEK expression was determined by immunohistochemistry in 67 formalin-fixed paraffin-embedded tumour samples from metastatic colorectal cancer patients treated with irinotecan-based therapy as first-line treatment.
  
  
  RESULTS
  The DEK oncogene is overexpressed in all colorectal cancer cell lines. Knock-down of DEK on DLD1 and SW620 cell lines decreased cell migration and increased irinotecan-induced apoptosis. In addition, low DEK expression level predicted irinotecan-based chemotherapy response in metastatic colorectal cancer patients with KRAS wild-type.
  
  
  CONCLUSIONS
  These data suggest DEK overexpression as a crucial event for the emergence of an aggressive phenotype in colorectal cancer and its potential role as biomarker for irinotecan response in those patients with KRAS wild-type status.
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Useros
authors.forename: Maria
authors.initials: M
authors.lastname: Rodriguez-Remirez
authors.forename: Aurea
authors.initials: A
authors.lastname: Borrero-Palacios
authors.forename: Irene
authors.initials: I
authors.lastname: Moreno
authors.forename: Arancha
authors.initials: A
authors.lastname: Cebrian
authors.forename: Teresa
authors.initials: T
authors.lastname: Gomez del Pulgar
authors.forename: Laura
authors.initials: L
authors.lastname: del Puerto-Nevado
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vega-Bravo
authors.forename: Alberto
authors.initials: A
authors.lastname: Puime-Otin
authors.forename: Nuria
authors.initials: N
authors.lastname: Perez
authors.forename: Sandra
authors.initials: S
authors.lastname: Zazo
authors.forename: Clara
authors.initials: C
authors.lastname: Senin
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Fernandez-Aceñero
authors.forename: Maria S
authors.initials: MS
authors.lastname: Soengas
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
authors.affiliation: Translational Oncology Division, OncoHealth Institute, Health Research Institute - University Hospital "Fundación Jiménez Díaz"-UAM, Av, Reyes Católicos 2, 28040 Madrid, Spain. jgfoncillas@gmail.com.
authors.forename: Jesus
authors.initials: J
authors.lastname: Garcia-Foncillas
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000502:physiology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000032:analysis / Q000502:physiology*; D010641:Phenotype; D000075223:Poly-ADP-Ribose Binding Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; C117307:KRAS protein, human; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002166:Camptothecin