Epigenetic upregulation of HGF and c-Met drives metastasis in hepatocellular carcinoma.
Epigenetic upregulation of HGF and c-Met drives metastasis in hepatocellular carcinoma.
复制标题
DOI：
10.1371/journal.pone.0063765
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Ogunwobi OO;Puszyk W;Dong HJ;Liu C
Hepatocyte growth factor (HGF) and its receptor, c-Met, are important regulators of growth and differentiation of healthy hepatocytes. However, upregulation of HGF and c-Met have been associated with tumor progression and metastasis in hepatocellular carcinoma (HCC). Hematogenous dissemination is the most common route for cancer metastasis, but the role of HGF and c-Met in circulating tumor cells (CTCs) is unknown. We have isolated and established a circulating tumor cell line from the peripheral blood of a mouse HCC model. Our studies show that these CTCs have increased expression of HGF and c-Met in comparison to the primary tumor cells. The CTCs display phenotypic evidence of epithelial-mesenchymal transition (EMT) and the EMT appears to be inducible by HGF. Epigenetic analysis of the c-Met promoter identified significant loss of DNA methylation in CTCs which correlated with overexpression of c-Met and increased expression of HGF. Six specific CpG sites of c-Met promoter demethylation were identified. CTCs show significantly increased tumorigenicity and metastatic potential in a novel orthotopic syngeneic model of metastatic HCC. We conclude that during hematogenous dissemination in HCC, CTCs undergo EMT under the influence of increased HGF. This process also involves up regulation of c-Met via promoter demethylation at 6 CpG sites. Consequently, targeting HGF and c-Met expression by CTCs may be a novel non-invasive approach with potential clinical applications in HCC management.
登录
查看更多内容
影响因子：
3.7
作者：
Konishi K;Watanabe Y;Shen L;Guo Y;Castoro RJ;Kondo K;Chung W;Ahmed S;Jelinek J;Boumber YA;Estecio MR;Maegawa S;Kondo Y;Itoh F;Imawari M;Hamilton SR;Issa JP
通讯作者：
Issa JP
影响因子：
4
作者：
Ogunwobi, Olorunseun O.;Liu, Chen
通讯作者：
Liu, Chen
影响因子：
13.5
作者：
Ding, Wei;You, Hanning;Dang, Hien;LeBlanc, Francis;Galicia, Vivian;Lu, Shelly C.;Stiles, Bangyan;Rountree, C. Bart
通讯作者：
Rountree, C. Bart
影响因子：
6
作者：
Liu, Hongyan;Dong, Huijia;Liu, Chen
通讯作者：
Liu, Chen
影响因子：
8
作者：
Morozov, V. M.;Massoll, N. A.;Ishov, A. M.
通讯作者：
Ishov, A. M.