title: Nuclear factor-κB-dependent epithelial to mesenchymal transition induced by HIF-1α activation in pancreatic cancer cells under hypoxic conditions.
abstract: BACKGROUND
  Epithelial to mesenchymal transition (EMT) induced by hypoxia is one of the critical causes of treatment failure in different types of human cancers. NF-κB is closely involved in the progression of EMT. Compared with HIF-1α, the correlation between NF-κB and EMT during hypoxia has been less studied, and although the phenomenon was observed in the past, the molecular mechanisms involved remained unclear.
  
  
  RESULTS
  Here, we report that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α) promotes EMT in pancreatic cancer cells. On molecular or pharmacologic inhibition of NF-κB, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and attenuated their highly invasive and drug-resistant phenotype. Introducing a pcDNA3.0/HIF-1α into pancreatic cancer cells under normoxic conditions heightened NF-κB activity, phenocopying EMT effects produced by hypoxia. Conversely, inhibiting the heightened NF-κB activity in this setting attenuated the EMT phenotype.
  
  
  CONCLUSIONS
  These results suggest that hypoxia or overexpression of HIF-1α induces the EMT that is largely dependent on NF-κB in pancreatic cancer cells.
authors: Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors: Zhuo-Xin
authors: ZX
authors: Cheng
authors: Bei
authors: B
authors: Sun
authors: Shuang-Jia
authors: SJ
authors: Wang
authors: Yue
authors: Y
authors: Gao
authors: Ying-Mei
authors: YM
authors: Zhang
authors: Hao-Xin
authors: HX
authors: Zhou
authors: Guang
authors: G
authors: Jia
authors: Yong-Wei
authors: YW
authors: Wang
authors: Rui
authors: R
authors: Kong
authors: Shang-Ha
authors: SH
authors: Pan
authors: Dong-Bo
authors: DB
authors: Xue
authors: Hong-Chi
authors: HC
authors: Jiang
authors: Xue-Wei
authors: XW
authors: Bai
mesh_terms: D015820:Cadherins; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B