Back to Search
Start Over
Nuclear Factor-&kgr;B-Dependent Epithelial to Mesenchymal Transition Induced by HIF-1&agr; Activation in Pancreatic Cancer Cells under Hypoxic Conditions.
- Source :
- PLoS ONE; 2011, Vol. 6 Issue 8, p1-11, 11p
- Publication Year :
- 2011
-
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-&kgr;B is closely involved in the progression of EMT. Compared with HIF-1&agr;, the correlation between NF-&kgr;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&agr; (HIF-1&agr;) promotes EMT in pancreatic cancer cells. On molecular or pharmacologic inhibition of NF-&kgr;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&agr; into pancreatic cancer cells under normoxic conditions heightened NF-&kgr;B activity, phenocopying EMT effects produced by hypoxia. Conversely, inhibiting the heightened NF-&kgr;B activity in this setting attenuated the EMT phenotype. Conclusions/Significance: These results suggest that hypoxia or overexpression of HIF-1&agr; induces the EMT that is largely dependent on NF-&kgr;B in pancreatic cancer cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 6
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 74399129
- Full Text :
- https://doi.org/10.1371/journal.pone.0023752