- 期刊
Epigenetic Regulation of EpCAM in Tumor Invasion and Metastasis
並列摘要
Metastatlc progression is the cause of most cancer decease. Many cell surface adhesion molecules are known to be present or re-expressed following gene promoter CpG island hypomethylation in the early stage of growing tumors, but absent or reduced by gene promoter CpG hypermethylation in metastasized carcinomas. Recent studies have revealed that an adhesion receptor, epithelial cell adhesion molecule (EpCAM), mediates cell-cell interaction and is involved in tumor invasion and metastasis. EpCAM expression was associated with promoter CpG methylatlon in lung adenocarclnoma. Treatment with a demethylating agent and histone deacetylase inhibitor reactivated EpCAM expression in EpCAM-negative cells and inhibited cancer cell invasiveness. Covalent histone tail modifications of histone H3 lysine 9 (H3K9), including acetylatlon or methylation, regulate these different states of chromatin configuration and gene transcription. Methylated and deacetylated H3K9 was present in the silenced EpCAM gene promoter of highly invasive cells, but it was largely decreased in the activated EpCAM gene promoter in low invasive cells. Despite EpCAM immunotherapy has been tested as a treatment modality for numerous cancers, the tumor-inhibitory mechanisms of anti-EpCAM antibodies still remain controversial. Since dynamic change of EpCAM expression is a regulatory event in the process of invasion or metastasis and DNA methylation is one of the major mechanisms in regulating EpCAM expression during this process, hypermethylated EpCAM gene promoter may serve as an invasiveness and progression marker for cancer diagnosis, prevention and treatment.
延伸閱讀
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