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

Biochem Biophys Res Commun. 2009 Oct 9;388(1):96-101. doi: 10.1016/j.bbrc.2009.07.125. Epub 2009 Jul 29.

Abstract

Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-kappaB 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-kappaB activation. Here, we show that the alternative pathway is constitutively activated and NF-kappaB-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Silencing
  • Humans
  • NF-kappa B p52 Subunit / metabolism*
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / pathology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Transcription Factor RelB / metabolism*

Substances

  • NF-kappa B p52 Subunit
  • RELB protein, human
  • Transcription Factor RelB
  • Protein-Serine-Threonine Kinases
  • NF-kappa B kinase