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PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression

Inflammatory breast cancer is a highly aggressive form of breast cancer that forms clusters of tumor emboli in dermal lymphatics and readily metastasizes. These cancers express high levels of E-cadherin, the major mediator of adherens junctions, which enhances formation of tumor emboli. Previous stu...

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Autores principales: Pence, Lindy J., Kourtidis, Antonis, Feathers, Ryan W., Haddad, Mary T., Sotiriou, Sotiris, Decker, Paul A., Nassar, Aziza, Ocal, Idris T., Shah, Sejal S., Anastasiadis, Panos Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865280/
https://www.ncbi.nlm.nih.gov/pubmed/33525380
http://dx.doi.org/10.3390/ijms22031275
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author Pence, Lindy J.
Kourtidis, Antonis
Feathers, Ryan W.
Haddad, Mary T.
Sotiriou, Sotiris
Decker, Paul A.
Nassar, Aziza
Ocal, Idris T.
Shah, Sejal S.
Anastasiadis, Panos Z.
author_facet Pence, Lindy J.
Kourtidis, Antonis
Feathers, Ryan W.
Haddad, Mary T.
Sotiriou, Sotiris
Decker, Paul A.
Nassar, Aziza
Ocal, Idris T.
Shah, Sejal S.
Anastasiadis, Panos Z.
author_sort Pence, Lindy J.
collection PubMed
description Inflammatory breast cancer is a highly aggressive form of breast cancer that forms clusters of tumor emboli in dermal lymphatics and readily metastasizes. These cancers express high levels of E-cadherin, the major mediator of adherens junctions, which enhances formation of tumor emboli. Previous studies suggest that E-cadherin promotes cancer when the balance between apical and basolateral cadherin complexes is disrupted. Here, we used immunohistochemistry of inflammatory breast cancer patient samples and analysis of cell lines to determine the expression of PLEKHA7, an apical adherens junction protein. We used viral transduction to re-express PLEKHA7 in inflammatory breast cancer cells and examined their aggressiveness in 2D and 3D cultures and in vivo. We determined that PLEKHA7 was deregulated in inflammatory breast cancer, demonstrating improper localization or lost expression in most patient samples and very low expression in cell lines. Re-expressing PLEKHA7 suppressed proliferation, anchorage independent growth, spheroid viability, and tumor growth in vivo. The data indicate that PLEKHA7 is frequently deregulated and acts to suppress inflammatory breast cancer. The data also promote the need for future inquiry into the imbalance between apical and basolateral cadherin complexes as driving forces in inflammatory breast cancer.
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spelling pubmed-78652802021-02-07 PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression Pence, Lindy J. Kourtidis, Antonis Feathers, Ryan W. Haddad, Mary T. Sotiriou, Sotiris Decker, Paul A. Nassar, Aziza Ocal, Idris T. Shah, Sejal S. Anastasiadis, Panos Z. Int J Mol Sci Article Inflammatory breast cancer is a highly aggressive form of breast cancer that forms clusters of tumor emboli in dermal lymphatics and readily metastasizes. These cancers express high levels of E-cadherin, the major mediator of adherens junctions, which enhances formation of tumor emboli. Previous studies suggest that E-cadherin promotes cancer when the balance between apical and basolateral cadherin complexes is disrupted. Here, we used immunohistochemistry of inflammatory breast cancer patient samples and analysis of cell lines to determine the expression of PLEKHA7, an apical adherens junction protein. We used viral transduction to re-express PLEKHA7 in inflammatory breast cancer cells and examined their aggressiveness in 2D and 3D cultures and in vivo. We determined that PLEKHA7 was deregulated in inflammatory breast cancer, demonstrating improper localization or lost expression in most patient samples and very low expression in cell lines. Re-expressing PLEKHA7 suppressed proliferation, anchorage independent growth, spheroid viability, and tumor growth in vivo. The data indicate that PLEKHA7 is frequently deregulated and acts to suppress inflammatory breast cancer. The data also promote the need for future inquiry into the imbalance between apical and basolateral cadherin complexes as driving forces in inflammatory breast cancer. MDPI 2021-01-28 /pmc/articles/PMC7865280/ /pubmed/33525380 http://dx.doi.org/10.3390/ijms22031275 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pence, Lindy J.
Kourtidis, Antonis
Feathers, Ryan W.
Haddad, Mary T.
Sotiriou, Sotiris
Decker, Paul A.
Nassar, Aziza
Ocal, Idris T.
Shah, Sejal S.
Anastasiadis, Panos Z.
PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression
title PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression
title_full PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression
title_fullStr PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression
title_full_unstemmed PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression
title_short PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression
title_sort plekha7, an apical adherens junction protein, suppresses inflammatory breast cancer in the context of high e-cadherin and p120-catenin expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865280/
https://www.ncbi.nlm.nih.gov/pubmed/33525380
http://dx.doi.org/10.3390/ijms22031275
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