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Roles for E-cadherin cell surface regulation in cancer

The loss of E-cadherin expression in association with the epithelial–mesenchymal transition (EMT) occurs frequently during tumor metastasis. However, metastases often retain E-cadherin expression, an EMT is not required for metastasis, and metastases can arise from clusters of tumor cells. We demons...

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Autores principales: Petrova, Yuliya I., Schecterson, Leslayann, Gumbiner, Barry M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170857/
https://www.ncbi.nlm.nih.gov/pubmed/27582386
http://dx.doi.org/10.1091/mbc.E16-01-0058
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author Petrova, Yuliya I.
Schecterson, Leslayann
Gumbiner, Barry M.
author_facet Petrova, Yuliya I.
Schecterson, Leslayann
Gumbiner, Barry M.
author_sort Petrova, Yuliya I.
collection PubMed
description The loss of E-cadherin expression in association with the epithelial–mesenchymal transition (EMT) occurs frequently during tumor metastasis. However, metastases often retain E-cadherin expression, an EMT is not required for metastasis, and metastases can arise from clusters of tumor cells. We demonstrate that the regulation of the adhesive activity of E-cadherin present at the cell surface by an inside-out signaling mechanism is important in cancer. First, we find that the metastasis of an E-cadherin–expressing mammary cell line from the mammary gland to the lung depends on reduced E-cadherin adhesive function. An activating monoclonal antibody to E-cadherin that induces a high adhesive state significantly reduced the number of cells metastasized to the lung without affecting the growth in size of the primary tumor in the mammary gland. Second, we find that many cancer-associated germline missense mutations in the E-cadherin gene in patients with hereditary diffuse gastric cancer selectively affect the mechanism of inside-out cell surface regulation without inhibiting basic E-cadherin adhesion function. This suggests that genetic deficits in E-cadherin cell surface regulation contribute to cancer progression. Analysis of these mutations also provides insights into the molecular mechanisms underlying cadherin regulation at the cell surface.
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spelling pubmed-51708572017-01-16 Roles for E-cadherin cell surface regulation in cancer Petrova, Yuliya I. Schecterson, Leslayann Gumbiner, Barry M. Mol Biol Cell Articles The loss of E-cadherin expression in association with the epithelial–mesenchymal transition (EMT) occurs frequently during tumor metastasis. However, metastases often retain E-cadherin expression, an EMT is not required for metastasis, and metastases can arise from clusters of tumor cells. We demonstrate that the regulation of the adhesive activity of E-cadherin present at the cell surface by an inside-out signaling mechanism is important in cancer. First, we find that the metastasis of an E-cadherin–expressing mammary cell line from the mammary gland to the lung depends on reduced E-cadherin adhesive function. An activating monoclonal antibody to E-cadherin that induces a high adhesive state significantly reduced the number of cells metastasized to the lung without affecting the growth in size of the primary tumor in the mammary gland. Second, we find that many cancer-associated germline missense mutations in the E-cadherin gene in patients with hereditary diffuse gastric cancer selectively affect the mechanism of inside-out cell surface regulation without inhibiting basic E-cadherin adhesion function. This suggests that genetic deficits in E-cadherin cell surface regulation contribute to cancer progression. Analysis of these mutations also provides insights into the molecular mechanisms underlying cadherin regulation at the cell surface. The American Society for Cell Biology 2016-11-01 /pmc/articles/PMC5170857/ /pubmed/27582386 http://dx.doi.org/10.1091/mbc.E16-01-0058 Text en © 2016 Petrova et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Petrova, Yuliya I.
Schecterson, Leslayann
Gumbiner, Barry M.
Roles for E-cadherin cell surface regulation in cancer
title Roles for E-cadherin cell surface regulation in cancer
title_full Roles for E-cadherin cell surface regulation in cancer
title_fullStr Roles for E-cadherin cell surface regulation in cancer
title_full_unstemmed Roles for E-cadherin cell surface regulation in cancer
title_short Roles for E-cadherin cell surface regulation in cancer
title_sort roles for e-cadherin cell surface regulation in cancer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170857/
https://www.ncbi.nlm.nih.gov/pubmed/27582386
http://dx.doi.org/10.1091/mbc.E16-01-0058
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