LSD1 通过维持 HIF1α 依赖性糖酵解过程来维持胰腺癌的生长。
LSD1 sustains pancreatic cancer growth via maintaining HIF1α-dependent glycolytic process.
机构信息
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.
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, PR China.
出版信息
Cancer Lett. 2014 Jun 1;347(2):225-32. doi: 10.1016/j.canlet.2014.02.013. Epub 2014 Feb 18.
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.
组蛋白去甲基化酶 LSD1（赖氨酸特异性去甲基酶 1）在基因转录的表观遗传调控中发挥重要作用。我们的研究调查了 LSD1 在胰腺癌中的作用，并证明 LSD1 在胰腺癌患者组织样本中显著上调，并且 LSD1 蛋白水平的升高与胰腺癌患者的总生存率呈正相关。通过体外和体内模型，我们证明敲低 LSD1 可抑制胰腺癌细胞的增殖和致瘤性。从机制上讲，我们的研究表明 LSD1 与 HIF1α（缺氧诱导因子 1α）协同作用，维持糖酵解过程，为胰腺癌的不受控制的增殖提供燃料。
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