The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer.
The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer.
复制标题
DOI：
10.3390/ijms19061695
复制
发表时间：
2018-06-07
影响因子：
5.6
通讯作者：
Watson CJ
中科院分区：
文献类型：
--
作者：
Hughes K;Watson CJ
自从信号转导子和转录激活子3（STAT 3）作为信号转导子和转录调节子（其最通常由特定酪氨酸残基的磷酸化激活）的开创性描述以来，大量的研究已经描绘了该转录因子作为乳腺泌乳后退化的介导者的关键作用（退化），矛盾的是，乳腺癌和一些乳腺癌细胞系中的促生存因子。STAT 3是乳腺退化期间溶酶体介导的程序性细胞死亡（LM-PCD）的关键调节剂，其中乳脂球的摄取以及随后的高水平游离脂肪酸引起溶酶体囊泡膜的透化，进而导致组织蛋白酶蛋白酶泄漏和细胞死亡。最近的蛋白质组学筛选STAT 3诱导的溶酶体膜蛋白组分的变化突出了STAT 3的广泛影响，其可以通过内吞作用、细胞内运输和溶酶体生物发生的刺激来协调LM-PCD。同时，STAT 3在退化的第一阶段期间调节急性期反应，并且它有助于在该过程的第二阶段期间形成腺体的促肿瘤“伤口愈合”特征。尽管奶牛退化过程中存在一些差异，但在退化过程中STAT 3的激活在不同物种中都很重要。在乳腺癌中，许多上游调节因子可导致STAT 3激活，STAT 3磷酸化的影响同样广泛。最近的研究表明microRNA参与了一些调控途径。在这篇综述中，我们将研究STAT 3在乳腺退化和肿瘤发生中的多方面作用，结合对这些基本过程的回顾，并讨论这一领域的最新进展。
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.
登录
查看更多内容
影响因子：
9
作者：
Hughes K;Blanck M;Pensa S;Watson CJ
通讯作者：
Watson CJ
DOI：
10.1073/pnas.0404100101
发表时间：
2004-07-20
影响因子：
11.1
作者：
Dechow, TN;Pedranzini, L;Bromberg, JF
通讯作者：
Bromberg, JF
影响因子：
2.4
作者：
Hughes, K.;Scase, T. J.;Foote, A. K.
通讯作者：
Foote, A. K.
影响因子：
10.5
作者：
Chapman, RS;Lourenco, PC;Watson, CJ
通讯作者：
Watson, CJ
影响因子：
2.5
作者：
Hughes K;Watson CJ
通讯作者：
Watson CJ