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Novel Role for γ-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1)
γ-catenin (Plakoglobin), a well-described structural protein functioning at the adherens junctions and desmosomes, was shown to be either lost or weakly expressed in non-small cell lung cancer (NSCLC) cells and tumor tissues. However, the tumor suppressive affects of γ-catenin were not fully underst...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505473/ https://www.ncbi.nlm.nih.gov/pubmed/25925948 http://dx.doi.org/10.1074/jbc.M114.631820 |
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author | Sechler, Marybeth Borowicz, Stanley Van Scoyk, Michelle Avasarala, Sreedevi Zerayesus, Sereke Edwards, Michael G. Kumar Karuppusamy Rathinam, Manoj Zhao, Xiangmin Wu, Pei-Ying Tang, Ke Bikkavilli, Rama Kamesh Winn, Robert A. |
author_facet | Sechler, Marybeth Borowicz, Stanley Van Scoyk, Michelle Avasarala, Sreedevi Zerayesus, Sereke Edwards, Michael G. Kumar Karuppusamy Rathinam, Manoj Zhao, Xiangmin Wu, Pei-Ying Tang, Ke Bikkavilli, Rama Kamesh Winn, Robert A. |
author_sort | Sechler, Marybeth |
collection | PubMed |
description | γ-catenin (Plakoglobin), a well-described structural protein functioning at the adherens junctions and desmosomes, was shown to be either lost or weakly expressed in non-small cell lung cancer (NSCLC) cells and tumor tissues. However, the tumor suppressive affects of γ-catenin were not fully understood. In this study, we have identified a novel role for the affects of γ-catenin on non-small cell lung cancer (NSCLC) cell migration. Expression of γ-catenin in NSCLC cells resulted in reduced cell migration as determined by both scratch assays and trans-well cell migration assays. Moreover, the affects of γ-catenin on cell migration were observed to be p53-dependent. Mechanistically, the anti-migratory effects seen via γ-catenin were driven by the expression of hepatocyte growth factor activator inhibitor Type I (HAI-1 or SPINT-1), an upstream inhibitor of the c-MET signaling pathway. Furthermore, the re-expression of γ-catenin sensitized NSCLC cells to c-MET inhibitor-mediated growth inhibition. Taken together, we identify γ-catenin as a novel regulator of HAI-1, which is a critical regulator of HGF/c-MET signaling. Therefore, targeting γ-catenin-mediated HAI-1 expression might be a useful strategy to sensitize NSCLC to c-MET inhibitors. |
format | Online Article Text |
id | pubmed-4505473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-45054732015-07-17 Novel Role for γ-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) Sechler, Marybeth Borowicz, Stanley Van Scoyk, Michelle Avasarala, Sreedevi Zerayesus, Sereke Edwards, Michael G. Kumar Karuppusamy Rathinam, Manoj Zhao, Xiangmin Wu, Pei-Ying Tang, Ke Bikkavilli, Rama Kamesh Winn, Robert A. J Biol Chem Molecular Bases of Disease γ-catenin (Plakoglobin), a well-described structural protein functioning at the adherens junctions and desmosomes, was shown to be either lost or weakly expressed in non-small cell lung cancer (NSCLC) cells and tumor tissues. However, the tumor suppressive affects of γ-catenin were not fully understood. In this study, we have identified a novel role for the affects of γ-catenin on non-small cell lung cancer (NSCLC) cell migration. Expression of γ-catenin in NSCLC cells resulted in reduced cell migration as determined by both scratch assays and trans-well cell migration assays. Moreover, the affects of γ-catenin on cell migration were observed to be p53-dependent. Mechanistically, the anti-migratory effects seen via γ-catenin were driven by the expression of hepatocyte growth factor activator inhibitor Type I (HAI-1 or SPINT-1), an upstream inhibitor of the c-MET signaling pathway. Furthermore, the re-expression of γ-catenin sensitized NSCLC cells to c-MET inhibitor-mediated growth inhibition. Taken together, we identify γ-catenin as a novel regulator of HAI-1, which is a critical regulator of HGF/c-MET signaling. Therefore, targeting γ-catenin-mediated HAI-1 expression might be a useful strategy to sensitize NSCLC to c-MET inhibitors. American Society for Biochemistry and Molecular Biology 2015-06-19 2015-04-29 /pmc/articles/PMC4505473/ /pubmed/25925948 http://dx.doi.org/10.1074/jbc.M114.631820 Text en © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/3.0) . |
spellingShingle | Molecular Bases of Disease Sechler, Marybeth Borowicz, Stanley Van Scoyk, Michelle Avasarala, Sreedevi Zerayesus, Sereke Edwards, Michael G. Kumar Karuppusamy Rathinam, Manoj Zhao, Xiangmin Wu, Pei-Ying Tang, Ke Bikkavilli, Rama Kamesh Winn, Robert A. Novel Role for γ-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) |
title | Novel Role for γ-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) |
title_full | Novel Role for γ-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) |
title_fullStr | Novel Role for γ-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) |
title_full_unstemmed | Novel Role for γ-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) |
title_short | Novel Role for γ-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) |
title_sort | novel role for γ-catenin in the regulation of cancer cell migration via the induction of hepatocyte growth factor activator inhibitor type 1 (hai-1) |
topic | Molecular Bases of Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505473/ https://www.ncbi.nlm.nih.gov/pubmed/25925948 http://dx.doi.org/10.1074/jbc.M114.631820 |
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