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

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

Author information

1
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, PR China.
2
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, PR China.
3
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, PR China. Electronic address: xjuin@163.com.
4
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, PR China. Electronic address: yuxianjun88@hotmail.com.

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

PMID:
24561118
DOI:
10.1016/j.canlet.2014.02.013
[Indexed for MEDLINE]
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