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

• LSD1 was frequently up-regulated in pancreatic cancer.
• LSD1 was associated with proliferation and tumorigenicity of pancreatic cancer cells.
• LSD1 regulated glycolysis in pancreatic cancer cells.
• LSD1 regulated HIF1α protein stability.
• LSD1 could be regulated by HIF1α.

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.