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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2015
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.
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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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