Mitochondrial dysfunction-induced amphiregulin upregulation mediates chemo-resistance and cell migration in HepG2 cells

C. J. Chang, P. H. Yin, D. M. Yang, C. H. Wang, W. Y. Hung, C. W. Chi, Y. H. Wei*, H. C. Lee

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

45 Scopus citations

Abstract

The aim of this study was to investigate the contribution of mitochondrial dysfunction to chemoresistance and migration of hepatoma cells. We found that inhibition of mitochondrial respiration and mitochondrial DNA (mtDNA) depletion resulted in induction of amphiregulin (AR) expression in HepG2 cells. Upon oligomycin treatment of HepG2 cells, the cytosolic Ca2+ was significantly raised after 30 min, and the intracellular level of reactive oxygen species (ROS) was elevated 2.2-fold after 4 h. Moreover, the condition medium of oligomycin-treated HepG2 cells was found to stimulate the migration of SK-Hep-1 cells. On the other hand, oligomycin-induced cisplatin-resistance and cell migration of HepG2 cells were attenuated by AR-specific RNA interference (#L-017435, Dharmacon) and a neutralizing antibody (MAB262, R&D Systems), respectively. Together, these findings suggest that mitochondrial dysfunction induced Ca2+ mobilization, and ROS overproduction, which modulated the chemo-resistance and migration of hepatoma cells through the induction and activation of AR.

Original languageEnglish
Pages (from-to)1755-1765
Number of pages11
JournalCellular and Molecular Life Sciences
Volume66
Issue number10
DOIs
StatePublished - 05 2009
Externally publishedYes

Keywords

  • ADAM17
  • Ca
  • EGFR
  • MtDNA depletion
  • Oligomycin
  • ROS

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