TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF Pathway

Laura D'Ignazio, Michael Batie, Sonia Rocha (Lead / Corresponding author)

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Abstract

Non-canonical NF-κB signalling plays important roles in the development and function of the immune system but it also is deregulated in a number of inflammatory diseases. Although, NF-κB and HIF crosstalk has been documented, this has only been described following canonical NF-κB stimulation, involving RelA/p50 and the HIF-1 dimer. Here, we report that the non-canonical inducer TNFSF14/LIGHT leads to HIF induction and activation in cancer cells. We demonstrate that only HIF-2α is induced at the transcriptional level following non-canonical NF-κB activation, via a mechanism that is dependent on the p52 subunit. Furthermore, we demonstrate that p52 can bind to the HIF-2α promoter in cells. These results indicate that non-canonical NF-κB can lead to HIF signalling implicating HIF-2α as one of the downstream effectors of this pathway in cells.

Original languageEnglish
Article number102
Pages (from-to)1-14
Number of pages14
JournalCells
Volume7
Issue number8
DOIs
Publication statusPublished - 8 Aug 2018

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Keywords

  • HIF
  • NF-κb
  • EPAS1
  • LIGHT
  • TNFSF14
  • p52
  • NIK
  • ChIP

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