TNF-α up-regulates cellular inhibitor of apoptosis protein 2 (c-IAP2) via c-Jun N-terminal kinase (JNK) pathway in nasopharyngeal carcinoma

Int Immunopharmacol. 2013 Jun;16(2):148-53. doi: 10.1016/j.intimp.2013.03.034. Epub 2013 Apr 15.

Abstract

Inhibitor of apoptosis proteins (IAPs) contribute to both tumor progression and tumor metastasis. Here, we show that pro-inflammatory cytokine TNF-α induced the up-regulation of c-IAP2 in the potential metastatic nasopharyngeal carcinoma (NPC) cells in a dose- and time-dependent manner. This up-regulation is tolerant, as the pre-treatment of NPC cells with TNF-α reversed the up-regulation of c-IAP2 induced by TNF-α re-stimulation. TNF-α activated MAKP signals, including ERK, JNK and p38, and NF-κB signal, but only inhibition of JNK signal transduction reversed the induction of c-IAP2, suggesting that JNK signaling contributed to the c-IAP2 induction. The results from in vitro scratch wound-healing assays showed that TNF-α promoted cell invasion, which was reversed by the inhibition of JNK signaling. Taken together, these studies suggested that pro-inflammation cytokine TNF-α may be a promoter for NPC metastasis, and the anti-inflammatory therapy may be of benefit to the prevention of NPC metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis*
  • Inhibitor of Apoptosis Proteins / genetics
  • MAP Kinase Signaling System / drug effects
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Up-Regulation

Substances

  • Inhibitor of Apoptosis Proteins
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha