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Heme oxygenase-1: a molecular brake on hepatocellular carcinoma cell migration.
- Source :
- Carcinogenesis; Dec2011, Vol. 32 Issue 12, p1840-1848, 9p
- Publication Year :
- 2011
-
Abstract
- Hepatocellular carcinoma (HCC) is a fatal disease with great public health impact worldwide. Heme oxygenase (HO)-1 has recently been reported as an important player in tumor angiogenesis and metastasis. However, the role of HO-1 in liver cancer metastasis is unclear. In this study, we explored genetic differences and downstream signal transduction pathways of HO-1 in liver cancer cell lines. HO-1 wild-type and mutant cell lines were generated from human liver cancer cell line HepG2. The overexpression of wild-type HO-1 decreased the migration of HepG2 cells. In contrast, the overexpression of mutant HO-1G143H increased the migration of the cancer cells. Interleukin (IL)-6 is one of the major downstream molecules that mediated this process because IL-6 expression and migration are suppressed by HO-1 and increased when HO-1 is knocked down by shRNA. In addition, we demonstrated carbon monoxide (CO) and p38MAPK are the cofactors in this signal pathway. In vivo animal model demonstrated HO-1 inhibited the tumor growth. In conclusion, in vitro and in vivo data show HO-1 inhibits the human HCC cells migration and tumor growth by suppressing the expression of IL-6. The heme degradation product CO is a cofactor in this process and inhibits p38MAPK phosphorylation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01433334
- Volume :
- 32
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 67381189
- Full Text :
- https://doi.org/10.1093/carcin/bgr225