Autor: |
Zhuo-Xin Cheng, Bei Sun, Shuang-Jia Wang, Yue Gao, Ying-Mei Zhang, Hao-Xin Zhou, Guang Jia, Yong-Wei Wang, Rui Kong, Shang-Ha Pan, Dong-Bo Xue, Hong-Chi Jiang, Xue-Wei Bai |
Jazyk: |
angličtina |
Rok vydání: |
2011 |
Předmět: |
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Zdroj: |
PLoS ONE, Vol 6, Iss 8, p e23752 (2011) |
Druh dokumentu: |
article |
ISSN: |
1932-6203 |
DOI: |
10.1371/journal.pone.0023752 |
Popis: |
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.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.These results suggest that hypoxia or overexpression of HIF-1α induces the EMT that is largely dependent on NF-κB in pancreatic cancer cells. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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