LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer

Br J Cancer. 2013 Aug 20;109(4):994-1003. doi: 10.1038/bjc.2013.364. Epub 2013 Jul 30.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics*
  • Antigens, CD / physiology
  • Apoptosis / genetics
  • Cadherins / genetics*
  • Cadherins / physiology
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Epigenesis, Genetic
  • HT29 Cells
  • Histone Demethylases / genetics*
  • Histone Demethylases / physiology
  • Histones / metabolism*
  • Humans
  • Neoplasm Invasiveness / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antigens, CD
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins
  • Histones
  • Histone Demethylases
  • KDM1A protein, human