J. Cancer Mol. 3:
165-168, 2008
[Review
Article]
Epigenetic Regulation of EpCAM in Tumor Invasion and Metastasis
Shine-Gwo
Shiah, Kang-Yu Tai, and Cheng-Wen Wu
National Institute of Cancer Research, National Health
Research Institutes, Zhunan Town, Miaoli County, Taiwan
Abstract:
Metastatic 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 methylation in lung adenocarcinoma. 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 acetylation 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.
(Keywords: EpCAM; invasion; promoter
methylation; epigenetic)
________________________________________________________________________________________________
Received 12/20/07; Revised
1/4/08; Accepted
1/6/08.
1Correspondence:
Dr. Cheng-Wen Wu, National Institute of Cancer Research, National Health
Research Institutes, No. 35, Keyan
Road, Zhunan Town, Miaoli County 350,
Taiwan, Republic of China. Phone: 886-37-246166 ext. 31701. Fax:
886-37-586463. E-mail:
881023@nhri.org.tw
2Abbreviations:
EpCAM,
epithelial cell adhesion molecule; H3K9, histone H3 lysine 9; HDAC,
histone deacetylase; TSA, trichostatin
A.
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