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Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix

SIMPLE SUMMARY: Current data suggest that epigenetic alterations are involved in the initiation and subclonal evolution of breast cancer. During cancer progression, the extracellular matrix undergoes significant structural alterations and the epithelial–mesenchymal transition is induced. These event...

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Autores principales: Zolota, Vasiliki, Tzelepi, Vasiliki, Piperigkou, Zoi, Kourea, Helen, Papakonstantinou, Efthymia, Argentou, Maria-Ioanna, Karamanos, Nikos K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916242/
https://www.ncbi.nlm.nih.gov/pubmed/33572395
http://dx.doi.org/10.3390/cancers13040713
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author Zolota, Vasiliki
Tzelepi, Vasiliki
Piperigkou, Zoi
Kourea, Helen
Papakonstantinou, Efthymia
Argentou, Maria-Ioanna
Karamanos, Nikos K.
author_facet Zolota, Vasiliki
Tzelepi, Vasiliki
Piperigkou, Zoi
Kourea, Helen
Papakonstantinou, Efthymia
Argentou, Maria-Ioanna
Karamanos, Nikos K.
author_sort Zolota, Vasiliki
collection PubMed
description SIMPLE SUMMARY: Current data suggest that epigenetic alterations are involved in the initiation and subclonal evolution of breast cancer. During cancer progression, the extracellular matrix undergoes significant structural alterations and the epithelial–mesenchymal transition is induced. These events among other processes are closely related with the epigenetic modifiers. Triple-negative breast cancer is an aggressive molecular subgroup characterized by genomic complexity and limited therapeutic options. Recent knowledge indicates that matrix alterations in triple-negative cancer cells are epigenetically regulated and that matrix-associated events collectively increase tumor cell survival and resistance to therapy. Thus, approaches for targeting tumor microenvironment and epigenetic pathways, alone or in combination, represent potential therapeutic strategies. The present article aims to highlight the most important epigenetic regulation of extracellular matrix alterations in triple-negative breast cancer in an effort to give perspectives for future design and implementation of diagnostic and therapeutic suggestions. ABSTRACT: Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer characterized by genomic complexity and therapeutic options limited to only standard chemotherapy. Although it has been suggested that stratifying TNBC patients by pathway-specific molecular alterations may predict benefit from specific therapeutic agents, application in routine clinical practice has not yet been established. There is a growing body of the literature supporting that epigenetic modifications comprised by DNA methylation, chromatin remodeling and non-coding RNAs play a fundamental role in TNBC pathogenesis. Extracellular matrix (ECM) is a highly dynamic 3D network of macromolecules with structural and cellular regulatory roles. Alterations in the expression of ECM components result in uncontrolled matrix remodeling, thus affecting its ability to regulate vital functions of cancer cells, including proliferation, migration, adhesion, invasion and epithelial-to-mesenchymal transition (EMT). Recent molecular data highlight the major role of tumor microenvironment and ECM alterations in TNBC and approaches for targeting tumor microenvironment have recently been recognized as potential therapeutic strategies. Notably, many of the ECM/EMT modifications in cancer are largely driven by epigenetic events, highlighting the pleiotropic effects of the epigenetic network in TNBC. This article presents and critically discusses the current knowledge on the epigenetic alterations correlated with TNBC pathogenesis, with emphasis on those associated with ECM/EMT modifications, their prognostic and predictive value and their use as therapeutic targets.
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spelling pubmed-79162422021-03-01 Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix Zolota, Vasiliki Tzelepi, Vasiliki Piperigkou, Zoi Kourea, Helen Papakonstantinou, Efthymia Argentou, Maria-Ioanna Karamanos, Nikos K. Cancers (Basel) Review SIMPLE SUMMARY: Current data suggest that epigenetic alterations are involved in the initiation and subclonal evolution of breast cancer. During cancer progression, the extracellular matrix undergoes significant structural alterations and the epithelial–mesenchymal transition is induced. These events among other processes are closely related with the epigenetic modifiers. Triple-negative breast cancer is an aggressive molecular subgroup characterized by genomic complexity and limited therapeutic options. Recent knowledge indicates that matrix alterations in triple-negative cancer cells are epigenetically regulated and that matrix-associated events collectively increase tumor cell survival and resistance to therapy. Thus, approaches for targeting tumor microenvironment and epigenetic pathways, alone or in combination, represent potential therapeutic strategies. The present article aims to highlight the most important epigenetic regulation of extracellular matrix alterations in triple-negative breast cancer in an effort to give perspectives for future design and implementation of diagnostic and therapeutic suggestions. ABSTRACT: Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer characterized by genomic complexity and therapeutic options limited to only standard chemotherapy. Although it has been suggested that stratifying TNBC patients by pathway-specific molecular alterations may predict benefit from specific therapeutic agents, application in routine clinical practice has not yet been established. There is a growing body of the literature supporting that epigenetic modifications comprised by DNA methylation, chromatin remodeling and non-coding RNAs play a fundamental role in TNBC pathogenesis. Extracellular matrix (ECM) is a highly dynamic 3D network of macromolecules with structural and cellular regulatory roles. Alterations in the expression of ECM components result in uncontrolled matrix remodeling, thus affecting its ability to regulate vital functions of cancer cells, including proliferation, migration, adhesion, invasion and epithelial-to-mesenchymal transition (EMT). Recent molecular data highlight the major role of tumor microenvironment and ECM alterations in TNBC and approaches for targeting tumor microenvironment have recently been recognized as potential therapeutic strategies. Notably, many of the ECM/EMT modifications in cancer are largely driven by epigenetic events, highlighting the pleiotropic effects of the epigenetic network in TNBC. This article presents and critically discusses the current knowledge on the epigenetic alterations correlated with TNBC pathogenesis, with emphasis on those associated with ECM/EMT modifications, their prognostic and predictive value and their use as therapeutic targets. MDPI 2021-02-09 /pmc/articles/PMC7916242/ /pubmed/33572395 http://dx.doi.org/10.3390/cancers13040713 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 Review
Zolota, Vasiliki
Tzelepi, Vasiliki
Piperigkou, Zoi
Kourea, Helen
Papakonstantinou, Efthymia
Argentou, Maria-Ioanna
Karamanos, Nikos K.
Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix
title Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix
title_full Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix
title_fullStr Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix
title_full_unstemmed Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix
title_short Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix
title_sort epigenetic alterations in triple-negative breast cancer—the critical role of extracellular matrix
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916242/
https://www.ncbi.nlm.nih.gov/pubmed/33572395
http://dx.doi.org/10.3390/cancers13040713
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