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STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context

Signal transducer and activator of transcription 3 (STAT3) is responsible for mediating the transcriptional programs downstream of several cytokine, growth factor, and oncogenic stimuli. Its expression and activity are consistently linked to cellular transformation, as well as tumor initiation and p...

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Detalles Bibliográficos
Autores principales: Segatto, Ilenia, Baldassarre, Gustavo, Belletti, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163512/
https://www.ncbi.nlm.nih.gov/pubmed/30231553
http://dx.doi.org/10.3390/ijms19092818
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author Segatto, Ilenia
Baldassarre, Gustavo
Belletti, Barbara
author_facet Segatto, Ilenia
Baldassarre, Gustavo
Belletti, Barbara
author_sort Segatto, Ilenia
collection PubMed
description Signal transducer and activator of transcription 3 (STAT3) is responsible for mediating the transcriptional programs downstream of several cytokine, growth factor, and oncogenic stimuli. Its expression and activity are consistently linked to cellular transformation, as well as tumor initiation and progression. Due to this central role, STAT3 is widely considered a good target for anti-cancer therapy; however, the success of these approaches has been, so far, very limited. Notably, on one side, STAT3 is aberrantly active in many breast cancers, on the other, at the physiological level, it is the main mediator of epithelial cell death during post-lactation mammary-gland involution, thus strongly suggesting that its biological functions are highly context-specific. One of the most peculiar features of STAT3 is that it can act both in cell-autonomous and non-cell-autonomous manners, simultaneously modulating the phenotypes of the tumor cells and their microenvironment. Here, we focus on the role of STAT3 in breast cancer progression, discussing the potential contrasting roles of STAT3 activation in the establishment of locally recurrent and distant metastatic disease. Based on the most recent literature, depending on the tumor cell type, the local microenvironment status, and the stage of the disease, either STAT3 activation or inactivation can support disease progression. Accordingly, cancer cells dynamically exploit STAT3 activity to carry out transcriptional programs somehow contrasting and complementary, such as supporting survival and growth, dormancy and awakening, stem cell-like features, and inflammation, immune response, and immune evasion. As a consequence, to achieve clinical efficacy, the conception and testing of anti-STAT3 targeted therapies will need a very careful evaluation of these opposing roles and of the most appropriate tumor context, disease stage and patient population to treat.
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spelling pubmed-61635122018-10-10 STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context Segatto, Ilenia Baldassarre, Gustavo Belletti, Barbara Int J Mol Sci Commentary Signal transducer and activator of transcription 3 (STAT3) is responsible for mediating the transcriptional programs downstream of several cytokine, growth factor, and oncogenic stimuli. Its expression and activity are consistently linked to cellular transformation, as well as tumor initiation and progression. Due to this central role, STAT3 is widely considered a good target for anti-cancer therapy; however, the success of these approaches has been, so far, very limited. Notably, on one side, STAT3 is aberrantly active in many breast cancers, on the other, at the physiological level, it is the main mediator of epithelial cell death during post-lactation mammary-gland involution, thus strongly suggesting that its biological functions are highly context-specific. One of the most peculiar features of STAT3 is that it can act both in cell-autonomous and non-cell-autonomous manners, simultaneously modulating the phenotypes of the tumor cells and their microenvironment. Here, we focus on the role of STAT3 in breast cancer progression, discussing the potential contrasting roles of STAT3 activation in the establishment of locally recurrent and distant metastatic disease. Based on the most recent literature, depending on the tumor cell type, the local microenvironment status, and the stage of the disease, either STAT3 activation or inactivation can support disease progression. Accordingly, cancer cells dynamically exploit STAT3 activity to carry out transcriptional programs somehow contrasting and complementary, such as supporting survival and growth, dormancy and awakening, stem cell-like features, and inflammation, immune response, and immune evasion. As a consequence, to achieve clinical efficacy, the conception and testing of anti-STAT3 targeted therapies will need a very careful evaluation of these opposing roles and of the most appropriate tumor context, disease stage and patient population to treat. MDPI 2018-09-18 /pmc/articles/PMC6163512/ /pubmed/30231553 http://dx.doi.org/10.3390/ijms19092818 Text en © 2018 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 Commentary
Segatto, Ilenia
Baldassarre, Gustavo
Belletti, Barbara
STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context
title STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context
title_full STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context
title_fullStr STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context
title_full_unstemmed STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context
title_short STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context
title_sort stat3 in breast cancer onset and progression: a matter of time and context
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163512/
https://www.ncbi.nlm.nih.gov/pubmed/30231553
http://dx.doi.org/10.3390/ijms19092818
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