Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis
<p>Abstract</p> <p>Background</p> <p>Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with ag...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-09-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | http://www.molecular-cancer.com/content/11/1/64 |
| _version_ | 1819177615321202688 |
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| author | Bozkaya Giray Korhan Peyda Çokaklı Murat Erdal Esra Sağol Özgül Karademir Sedat Korch Christopher Atabey Neşe |
| author_facet | Bozkaya Giray Korhan Peyda Çokaklı Murat Erdal Esra Sağol Özgül Karademir Sedat Korch Christopher Atabey Neşe |
| author_sort | Bozkaya Giray |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis.</p> <p>Results</p> <p>MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion.</p> <p>Conclusions</p> <p>These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.</p> |
| first_indexed | 2024-12-22T21:29:28Z |
| format | Article |
| id | doaj.art-2426d3e8fde44d439226122b60f69f94 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-22T21:29:28Z |
| publishDate | 2012-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-2426d3e8fde44d439226122b60f69f942022-12-21T18:11:58ZengBMCMolecular Cancer1476-45982012-09-011116410.1186/1476-4598-11-64Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesisBozkaya GirayKorhan PeydaÇokaklı MuratErdal EsraSağol ÖzgülKarademir SedatKorch ChristopherAtabey Neşe<p>Abstract</p> <p>Background</p> <p>Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis.</p> <p>Results</p> <p>MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion.</p> <p>Conclusions</p> <p>These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.</p>http://www.molecular-cancer.com/content/11/1/64Hepatocellular carcinoma (HCC)Hepatocyte Growth Factor (HGF)/c-MetMucin 1 (MUC1)DifferentiationInvasion |
| spellingShingle | Bozkaya Giray Korhan Peyda Çokaklı Murat Erdal Esra Sağol Özgül Karademir Sedat Korch Christopher Atabey Neşe Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis Molecular Cancer Hepatocellular carcinoma (HCC) Hepatocyte Growth Factor (HGF)/c-Met Mucin 1 (MUC1) Differentiation Invasion |
| title | Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis |
| title_full | Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis |
| title_fullStr | Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis |
| title_full_unstemmed | Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis |
| title_short | Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis |
| title_sort | cooperative interaction of muc1 with the hgf c met pathway during hepatocarcinogenesis |
| topic | Hepatocellular carcinoma (HCC) Hepatocyte Growth Factor (HGF)/c-Met Mucin 1 (MUC1) Differentiation Invasion |
| url | http://www.molecular-cancer.com/content/11/1/64 |
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