Constitutive NF-κB activation and tumor-growth promotion by Romo1-mediated reactive oxygen species production

Jin Sil Chung, Sora Lee, Young Do Yoo

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Deregulation of nuclear factor-κB (NF-κB) and related pathways contribute to tumor cell proliferation and invasion. Mechanisms for constitutive NF-κB activation are not fully explained; however, the underlying defects appear to generate and maintain pro-oxidative conditions. In hepatocellular carcinoma (HCC) tissues, up-regulation of reactive oxygen species modulator 1 (Romo1) correlates positively with tumor size. In the present study, we showed that Romo1 expression is required to maintain constitutive nuclear DNA-binding activity of NF-κB and transcriptional activity through constitutive IκBα phosphorylation. Overexpression of Romo1 promoted p65 nuclear translocation and DNA-binding activity. We also show that Romo1 depletion suppressed anchorage-independent colony formation by HCC cells and suppressed tumor growth in vivo. Based on these findings, Romo1 may be a principal regulatory factor in the maintenance of constitutive NF-κB activation in tumor cells. In the interest of anti-proliferative treatments for cancer, Romo1 may also present a productive target for drug development.

Original languageEnglish
Pages (from-to)1656-1661
Number of pages6
JournalBiochemical and biophysical research communications
Volume450
Issue number4
DOIs
Publication statusPublished - 2014 Aug 8

Keywords

  • Hepatocellular carcinoma
  • Nuclear factor-kappa B
  • Oxidative stress
  • Reactive oxygen species
  • Romo1
  • Tumor growth

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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