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Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial–Mesenchymal Plasticity

SIMPLE SUMMARY: Epithelial–mesenchymal transition (EMT) and its reverse process mesenchymal–epithelial transition (MET) are considered critical events in the cancer progression. These programs are tightly connected with the development of metastasis–the lethal stage of the disease. Both EMT and MET...

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Autores principales: Kvokačková, Barbora, Remšík, Ján, Jolly, Mohit Kumar, Souček, Karel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125677/
https://www.ncbi.nlm.nih.gov/pubmed/34063254
http://dx.doi.org/10.3390/cancers13092188
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author Kvokačková, Barbora
Remšík, Ján
Jolly, Mohit Kumar
Souček, Karel
author_facet Kvokačková, Barbora
Remšík, Ján
Jolly, Mohit Kumar
Souček, Karel
author_sort Kvokačková, Barbora
collection PubMed
description SIMPLE SUMMARY: Epithelial–mesenchymal transition (EMT) and its reverse process mesenchymal–epithelial transition (MET) are considered critical events in the cancer progression. These programs are tightly connected with the development of metastasis–the lethal stage of the disease. Both EMT and MET shape the biology of unusually aggressive and heterogeneous triple-negative breast cancer (TNBC). In this review, we summarize the current knowledge of EMT/MET plasticity in the context of TNBC, with a special focus on drivers and mechanisms behind these processes. ABSTRACT: Triple-negative breast cancer (TNBC) is a subtype of breast carcinoma known for its unusually aggressive behavior and poor clinical outcome. Besides the lack of molecular targets for therapy and profound intratumoral heterogeneity, the relatively quick overt metastatic spread remains a major obstacle in effective clinical management. The metastatic colonization of distant sites by primary tumor cells is affected by the microenvironment, epigenetic state of particular subclones, and numerous other factors. One of the most prominent processes contributing to the intratumoral heterogeneity is an epithelial–mesenchymal transition (EMT), an evolutionarily conserved developmental program frequently hijacked by tumor cells, strengthening their motile and invasive features. In response to various intrinsic and extrinsic stimuli, malignant cells can revert the EMT state through the mesenchymal–epithelial transition (MET), a process that is believed to be critical for the establishment of macrometastasis at secondary sites. Notably, cancer cells rarely undergo complete EMT and rather exist in a continuum of E/M intermediate states, preserving high levels of plasticity, as demonstrated in primary tumors and, ultimately, in circulating tumor cells, representing a simplified element of the metastatic cascade. In this review, we focus on cellular drivers underlying EMT/MET phenotypic plasticity and its detrimental consequences in the context of TNBC cancer.
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spelling pubmed-81256772021-05-17 Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial–Mesenchymal Plasticity Kvokačková, Barbora Remšík, Ján Jolly, Mohit Kumar Souček, Karel Cancers (Basel) Review SIMPLE SUMMARY: Epithelial–mesenchymal transition (EMT) and its reverse process mesenchymal–epithelial transition (MET) are considered critical events in the cancer progression. These programs are tightly connected with the development of metastasis–the lethal stage of the disease. Both EMT and MET shape the biology of unusually aggressive and heterogeneous triple-negative breast cancer (TNBC). In this review, we summarize the current knowledge of EMT/MET plasticity in the context of TNBC, with a special focus on drivers and mechanisms behind these processes. ABSTRACT: Triple-negative breast cancer (TNBC) is a subtype of breast carcinoma known for its unusually aggressive behavior and poor clinical outcome. Besides the lack of molecular targets for therapy and profound intratumoral heterogeneity, the relatively quick overt metastatic spread remains a major obstacle in effective clinical management. The metastatic colonization of distant sites by primary tumor cells is affected by the microenvironment, epigenetic state of particular subclones, and numerous other factors. One of the most prominent processes contributing to the intratumoral heterogeneity is an epithelial–mesenchymal transition (EMT), an evolutionarily conserved developmental program frequently hijacked by tumor cells, strengthening their motile and invasive features. In response to various intrinsic and extrinsic stimuli, malignant cells can revert the EMT state through the mesenchymal–epithelial transition (MET), a process that is believed to be critical for the establishment of macrometastasis at secondary sites. Notably, cancer cells rarely undergo complete EMT and rather exist in a continuum of E/M intermediate states, preserving high levels of plasticity, as demonstrated in primary tumors and, ultimately, in circulating tumor cells, representing a simplified element of the metastatic cascade. In this review, we focus on cellular drivers underlying EMT/MET phenotypic plasticity and its detrimental consequences in the context of TNBC cancer. MDPI 2021-05-02 /pmc/articles/PMC8125677/ /pubmed/34063254 http://dx.doi.org/10.3390/cancers13092188 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kvokačková, Barbora
Remšík, Ján
Jolly, Mohit Kumar
Souček, Karel
Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial–Mesenchymal Plasticity
title Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial–Mesenchymal Plasticity
title_full Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial–Mesenchymal Plasticity
title_fullStr Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial–Mesenchymal Plasticity
title_full_unstemmed Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial–Mesenchymal Plasticity
title_short Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial–Mesenchymal Plasticity
title_sort phenotypic heterogeneity of triple-negative breast cancer mediated by epithelial–mesenchymal plasticity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125677/
https://www.ncbi.nlm.nih.gov/pubmed/34063254
http://dx.doi.org/10.3390/cancers13092188
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