Nuclear factor-κB-dependent epithelial to mesenchymal transition induced by HIF-1α activation in pancreatic cancer cells under hypoxic conditions.

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:
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.
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