title: LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer.
abstract: BACKGROUND
  Emerging evidence has demonstrated that lysine-specific demethylase 1 (LSD1) has an important role in many pathological processes of cancer cells, such as carcinogenesis, proliferation and metastasis. In this study, we characterised the role and molecular mechanisms of LSD1 in proliferation and metastasis of colon cancer.
  
  
  METHODS
  We evaluated the correlation of LSD1, CDH-1 and CDH-2 with invasiveness of colon cancer cells, and investigated the roles of LSD1 in proliferation, invasion and apoptosis of colon cancer cells. We further investigated the mechanisms of LSD1-mediated metastasis of colon cancer.
  
  
  RESULTS
  Lysine-specific demethylase 1 was upregulated in colon cancer tissues, and the high LSD1 expression was significantly associated with tumour-node-metastasis (TNM) stages and distant metastasis. Functionally, inhibition of LSD1 impaired proliferation and invasiveness, and induced apoptosis of colon cancer cells in vitro. The LSD1 physically interacted with the promoter of CDH-1 and decreased dimethyl histone H3 lysine 4 (H3K4) at this region, downregulated CDH-1 expression, and consequently contributed to colon cancer metastasis.
  
  
  CONCLUSIONS
  Lysine-specific demethylase 1 downregulates the expression of CDH-1 by epigenetic modification, and consequently promotes metastasis of colon cancer cells. The LSD1 antagonists might be a useful strategy to suppress metastasis of colon cancer.
authors.affiliation: Department of Gastrointestinal Surgery, Guizhou Provincial People's Hospital, Guiyang, China. dingjieboy@126.com
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.forename: Z-M
authors.initials: ZM
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: G-Q
authors.initials: GQ
authors.lastname: Liao
authors.forename: Y
authors.initials: Y
authors.lastname: Pan
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Z-S
authors.initials: ZS
authors.lastname: Yan
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D044127:Epigenesis, Genetic; D019073:HT29 Cells; D056466:Histone Demethylases / Q000235:genetics* / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D006657:Histones; D056466:Histone Demethylases; C495195:KDM1A protein, human
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