LSD1 sustains pancreatic cancer growth via maintaining HIF1α-dependent glycolytic process

Cancer Lett. 2014 Jun 1;347(2):225-32. doi: 10.1016/j.canlet.2014.02.013. Epub 2014 Feb 18.

Abstract

The histone demethylase LSD1 (lysine specific demethylase 1) plays an important role in the epigenetic regulation of gene transcription. Our study investigated the role of LSD1 in pancreatic cancer and demonstrated that LSD1 was significantly up-regulated in pancreatic cancer patient tissue samples, and elevated LSD1 protein levels positively correlated with overall survival of pancreatic cancer patients. Using in vitro and in vivo models, we demonstrated that knock-down of LSD1 repressed proliferation and tumorigenicity of pancreatic cancer cells. Mechanistically, our study demonstrated that LSD1 synergized with HIF1α (hypoxia inducible factor-1α) in maintaining glycolytic process, which fueled pancreatic cancer uncontrolled proliferation.

Keywords: Glycolysis; HIF1α; LSD1; Pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers
  • Female
  • Glycolysis
  • Histone Demethylases / genetics
  • Histone Demethylases / physiology*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / physiology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • RNA Interference
  • Real-Time Polymerase Chain Reaction

Substances

  • DNA Primers
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Histone Demethylases
  • KDM1A protein, human