The prolyl isomerase Pin1 regulates the NF-kappaB signaling pathway and interleukin-8 expression in glioblastoma

Oncogene. 2009 Oct 22;28(42):3735-45. doi: 10.1038/onc.2009.232. Epub 2009 Aug 10.


The brain tumor glioblastoma (GBM) remains one of the most aggressive and devastating tumors despite decades of effort to find more effective treatments. A hallmark of GBM is the constitutive activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling pathway, which regulates cell proliferation, inflammation, migration and apoptosis. The prolyl isomerase, Pin1, has been found to bind directly to the NF-kappaB protein, p65, and cause increases in NF-kappaB promoter activity in a breast cancer model. We now present evidence that this interaction occurs in GBM and that it has important consequences on NF-kappaB signaling. We demonstrate that Pin1 levels are enhanced in primary GBM tissues compared with controls, and that this difference in Pin1 expression affects the migratory capacity of GBM-derived cells. Pin1 knockdown decreases the amount of activated, phosphorylated p65 in the nucleus, resulting in inhibition of the transcriptional program of the IL-8 gene. Through the use of microarray, we also observed changes in the expression levels of other NF-kappaB regulated genes due to Pin1 knockdown. Taken together, these data suggest that Pin1 is an important regulator of NF-kappaB in GBM, and support the notion of using Pin1 as a therapeutic target in the future.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Gene Knockdown Techniques
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Interleukin-8 / genetics*
  • Inverted Repeat Sequences
  • Mice
  • NF-kappa B / metabolism*
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptidylprolyl Isomerase / deficiency
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Phosphorylation
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction*
  • Tetracycline / pharmacology
  • Transcription Factor RelA / metabolism


  • Interleukin-8
  • NF-kappa B
  • NIMA-Interacting Peptidylprolyl Isomerase
  • RNA, Messenger
  • Transcription Factor RelA
  • PIN1 protein, human
  • Peptidylprolyl Isomerase
  • Pin1 protein, mouse
  • Tetracycline