NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells

Takashi Nishina, Noritaka Yamaguchi, Jin Gohda, Kentaro Semba, Jun ichiro Inoue

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-κB is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-κB activation. Here, we show that the alternative pathway is constitutively activated and NF-κB-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

Original languageEnglish
Pages (from-to)96-101
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume388
Issue number1
DOIs
Publication statusPublished - 2009 Oct 9

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Keywords

  • Alternative pathway
  • IKKα
  • NIK
  • Pancreatic cancer
  • RelB

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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