title: VEGF Promotes Glycolysis in Pancreatic Cancer via HIF1α Up-Regulation.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) is highly expressed in many types of tumors, including pancreatic cancer. Tumor cellderived VEGF promotes angiogenesis and tumor progression. However, the role of VEGF in glucose metabolism remains unclear.
  
  
  OBJECTIVE
  We investigated the role and the underlying mechanism of VEGF in the glucose metabolism of pancreatic cancer cells.
  
  
  METHODS
  Pancreatic cancer cells were stimulated with VEGF165 for 1 or 2 h. The oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) were measured using the Seahorse XF96 Extracellular Flux Analyzer. Glycolytic enzymes were detected by quantitative real-time PCR. Neuropilin 1 (NRP1) was silenced by shRNA in order to investigate its role in VEGF-induced glycolysis. Immunohistochemistry (IHC) was performed to identify the correlation among VEGF, NRP1 and hypoxia inducible factor 1α (HIF1α) in pancreatic cancer tissues.
  
  
  RESULTS
  VEGF stimulation led to a metabolic transition from mitochondrial oxidative phosphorylation to glycolysis in pancreatic cancer. HIF1α and NRP1 protein levels were both increased after VEGF stimulation. The down-regulation of NRP1 reduced glycolysis in pancreatic cancer cells. NRP1 and VEGF levels both correlated with HIF1α expression in pancreatic tumor tissues.
  
  
  CONCLUSIONS
  VEGF enhances glycolysis in pancreatic cancer via HIF1α up-regulation. NRP1 plays a key role in VEGF-induced glycolysis.
authors.forename: S
authors.initials: S
authors.lastname: Shi
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: B
authors.initials: B
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Ji
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: K
authors.initials: K
authors.lastname: Jin
authors.forename: D
authors.initials: D
authors.lastname: Liang
authors.forename: C
authors.initials: C
authors.lastname: Liang
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, 270 DongAn Road, Shanghai 200032, China. qinyi@fudanpci.org.
authors.forename: Y
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, 270 DongAn Road, Shanghai 200032, China. yuxianjun88@hotmail.com.
authors.forename: X
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008954:Models, Biological; D039942:Neuropilin-1 / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D005947:Glucose