Journal
PLOS ONE
Volume 6, Issue 8, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0023752
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Funding
- New Century Support Foundation for Elitist of Chinese Ministry of Education [NCET-07-0248]
- Scientific Foundation for Prominent Youth of Heilongjiang Province, China [JC200717]
- Scientific and Technological Project of Heilongjiang Province, China [GC09C407-2]
- National Natural Scientific Foundation of China [30571808, 30872987]
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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-kappa B is closely involved in the progression of EMT. Compared with HIF-1 alpha, the correlation between NF-kappa B and EMT during hypoxia has been less studied, and although the phenomenon was observed in the past, the molecular mechanisms involved remained unclear. Methodology/Principal Findings: Here, we report that hypoxia or overexpression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) promotes EMT in pancreatic cancer cells. On molecular or pharmacologic inhibition of NF-kappa B, 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-1 alpha into pancreatic cancer cells under normoxic conditions heightened NF-kappa B activity, phenocopying EMT effects produced by hypoxia. Conversely, inhibiting the heightened NF-kappa B activity in this setting attenuated the EMT phenotype. Conclusions/Significance: These results suggest that hypoxia or overexpression of HIF-1 alpha induces the EMT that is largely dependent on NF-kappa B in pancreatic cancer cells.
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