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 language | English |
|---|---|
| Pages (from-to) | 1656-1661 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 450 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2014 Aug 8 |
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ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
- Molecular Biology
Cite this
Constitutive NF-κB activation and tumor-growth promotion by Romo1-mediated reactive oxygen species production. / Chung, Jin Sil; Lee, Sora; Yoo, Young Do.
In: Biochemical and Biophysical Research Communications, Vol. 450, No. 4, 08.08.2014, p. 1656-1661.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Constitutive NF-κB activation and tumor-growth promotion by Romo1-mediated reactive oxygen species production
AU - Chung, Jin Sil
AU - Lee, Sora
AU - Yoo, Young Do
PY - 2014/8/8
Y1 - 2014/8/8
N2 - 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.
AB - 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.
KW - Hepatocellular carcinoma
KW - Nuclear factor-kappa B
KW - Oxidative stress
KW - Reactive oxygen species
KW - Romo1
KW - Tumor growth
UR - http://www.scopus.com/inward/record.url?scp=84906089429&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906089429&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2014.07.059
DO - 10.1016/j.bbrc.2014.07.059
M3 - Article
VL - 450
SP - 1656
EP - 1661
JO - The BMJ
JF - The BMJ
SN - 0730-6512
IS - 4
ER -