Requirement of T-lymphokine-activated killer cell-originated protein kinase for TRAIL resistance of human HeLa cervical cancer cells

Hyeok Ran Kwon, Ki Won Lee, Zigang Dong, Kyung Bok Lee, Sang Muk Oh

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

T-lymphokine-activated killer cell-originated protein kinase (TOPK) appears to be highly expressed in various cancer cells and to play an important role in maintaining proliferation of cancer cells. However, the underlying mechanism by which TOPK regulates growth of cancer cells remains elusive. Here we report that upregulated endogenous TOPK augments resistance of cancer cells to apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Stable knocking down of TOPK markedly increased TRAIL-mediated apoptosis of human HeLa cervical cancer cells, as compared with control cells. Caspase 8 or caspase 3 activities in response to TRAIL were greatly incremented in TOPK-depleted cells. Ablation of TOPK negatively regulated TRAIL-mediated NF-κB activity. Furthermore, expression of NF-κB-dependent genes, FLICE-inhibitory protein (FLIP), inhibitor of apoptosis protein 1 (c-IAP1), or X-linked inhibitor of apoptosis protein (XIAP) was reduced in TOPK-depleted cells. Collectively, these findings demonstrated that TOPK contributed to TRAIL resistance of cancer cells via NF-κB activity, suggesting that TOPK might be a potential molecular target for successful cancer therapy using TRAIL.

Original languageEnglish (US)
Pages (from-to)830-834
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume391
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • Apoptosis
  • Caspase
  • NF-κB
  • TOPK
  • TRAIL

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