Cargando…

The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer

Since seminal descriptions of signal transducer and activator of transcription 3 (STAT3) as a signal transducer and transcriptional regulator, which is most usually activated by phosphorylation of a specific tyrosine residue, a staggering wealth of research has delineated the key role of this transc...

Descripción completa

Detalles Bibliográficos
Autores principales: Hughes, Katherine, Watson, Christine J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032292/
https://www.ncbi.nlm.nih.gov/pubmed/29875329
http://dx.doi.org/10.3390/ijms19061695
_version_ 1783337479719354368
author Hughes, Katherine
Watson, Christine J.
author_facet Hughes, Katherine
Watson, Christine J.
author_sort Hughes, Katherine
collection PubMed
description Since seminal descriptions of signal transducer and activator of transcription 3 (STAT3) as a signal transducer and transcriptional regulator, which is most usually activated by phosphorylation of a specific tyrosine residue, a staggering wealth of research has delineated the key role of this transcription factor as a mediator of mammary gland postlactational regression (involution), and paradoxically, a pro-survival factor in breast cancer and some breast cancer cell lines. STAT3 is a critical regulator of lysosomal-mediated programmed cell death (LM-PCD) during mammary gland involution, where uptake of milk fat globules, and consequent high levels of free fatty acids, cause permeabilisation of lysosomal vesicle membranes, in turn leading to cathepsin protease leakage and cell death. A recent proteomic screen of STAT3-induced changes in lysosomal membrane protein components has highlighted wide-ranging effects of STAT3, which may coordinate LM-PCD via the stimulation of endocytosis, intracellular trafficking, and lysosome biogenesis. In parallel, STAT3 regulates the acute phase response during the first phase of involution, and it contributes to shaping the pro-tumourigenic ‘wound healing’ signature of the gland during the second phase of this process. STAT3 activation during involution is important across species, although some differences exist in the progression of involution in dairy cows. In breast cancer, a number of upstream regulators can lead to STAT3 activation and the effects of phosphorylation of STAT3 are equally wide-ranging. Recent studies have implicated microRNAs in some regulatory pathways. In this review, we will examine the multifaceted role of STAT3 in mammary gland involution and tumourigenesis, incorporating a review of these fundamental processes in tandem with a discussion of recent developments in this field.
format Online
Article
Text
id pubmed-6032292
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-60322922018-07-13 The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer Hughes, Katherine Watson, Christine J. Int J Mol Sci Review Since seminal descriptions of signal transducer and activator of transcription 3 (STAT3) as a signal transducer and transcriptional regulator, which is most usually activated by phosphorylation of a specific tyrosine residue, a staggering wealth of research has delineated the key role of this transcription factor as a mediator of mammary gland postlactational regression (involution), and paradoxically, a pro-survival factor in breast cancer and some breast cancer cell lines. STAT3 is a critical regulator of lysosomal-mediated programmed cell death (LM-PCD) during mammary gland involution, where uptake of milk fat globules, and consequent high levels of free fatty acids, cause permeabilisation of lysosomal vesicle membranes, in turn leading to cathepsin protease leakage and cell death. A recent proteomic screen of STAT3-induced changes in lysosomal membrane protein components has highlighted wide-ranging effects of STAT3, which may coordinate LM-PCD via the stimulation of endocytosis, intracellular trafficking, and lysosome biogenesis. In parallel, STAT3 regulates the acute phase response during the first phase of involution, and it contributes to shaping the pro-tumourigenic ‘wound healing’ signature of the gland during the second phase of this process. STAT3 activation during involution is important across species, although some differences exist in the progression of involution in dairy cows. In breast cancer, a number of upstream regulators can lead to STAT3 activation and the effects of phosphorylation of STAT3 are equally wide-ranging. Recent studies have implicated microRNAs in some regulatory pathways. In this review, we will examine the multifaceted role of STAT3 in mammary gland involution and tumourigenesis, incorporating a review of these fundamental processes in tandem with a discussion of recent developments in this field. MDPI 2018-06-07 /pmc/articles/PMC6032292/ /pubmed/29875329 http://dx.doi.org/10.3390/ijms19061695 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 Review
Hughes, Katherine
Watson, Christine J.
The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer
title The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer
title_full The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer
title_fullStr The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer
title_full_unstemmed The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer
title_short The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer
title_sort multifaceted role of stat3 in mammary gland involution and breast cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032292/
https://www.ncbi.nlm.nih.gov/pubmed/29875329
http://dx.doi.org/10.3390/ijms19061695
work_keys_str_mv AT hugheskatherine themultifacetedroleofstat3inmammaryglandinvolutionandbreastcancer
AT watsonchristinej themultifacetedroleofstat3inmammaryglandinvolutionandbreastcancer
AT hugheskatherine multifacetedroleofstat3inmammaryglandinvolutionandbreastcancer
AT watsonchristinej multifacetedroleofstat3inmammaryglandinvolutionandbreastcancer