Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
PLoS One. 2011;6(8):e23752. doi: 10.1371/journal.pone.0023752. Epub 2011 Aug 22.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: These results suggest that hypoxia or overexpression of HIF-1α induces the EMT that is largely dependent on NF-κB in pancreatic cancer cells.
缺氧诱导的上皮间质转化（EMT）是导致不同类型人类癌症治疗失败的关键原因之一。NF-κB 密切参与 EMT 的进展。与 HIF-1α 相比，NF-κB 与缺氧时 EMT 之间的相关性研究较少，尽管过去观察到了这种现象，但涉及的分子机制仍不清楚。
方法/主要发现：在这里，我们报告缺氧或过表达缺氧诱导因子-1α（HIF-1α）可促进胰腺癌细胞发生 EMT。在分子或药理学上抑制 NF-κB，缺氧细胞恢复了 E-钙黏蛋白的表达，失去了 N-钙黏蛋白的表达，并减弱了其高度侵袭性和耐药表型。在常氧条件下将 pcDNA3.0/HIF-1α 导入胰腺癌细胞会提高 NF-κB 的活性，模拟缺氧产生的 EMT 效应。相反，在这种情况下抑制 NF-κB 活性的升高会减弱 EMT 表型。
结论/意义：这些结果表明，缺氧或 HIF-1α 的过表达诱导 EMT，在胰腺癌细胞中 EMT 主要依赖于 NF-κB。
