Obesity and Androgen Receptor Signaling: Associations and Potential Crosstalk in Breast Cancer Cells.
Obesity and Androgen Receptor Signaling: Associations and Potential Crosstalk in Breast Cancer Cells.
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DOI：
10.3390/cancers13092218
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发表时间：
2021-05-06
期刊：
影响因子：
5.2
通讯作者：
Rondón-Lagos M
中科院分区：
文献类型：
--
作者：
Rangel N;Villegas VE;Rondón-Lagos M
尽管越来越多的信息表明肥胖是一个重要的乳腺癌（BC）危险因素，但这种关联的机制尚不清楚。在这篇综述中，我们描述了多种证据，表明功能失调的脂肪组织中雄激素和脂肪因子分泌的改变与BC的发展独立相关。然而，脂肪因子（脂联素和瘦素）通过调节类似于雄激素受体使用的信号通路参与BC细胞的重要生物学过程。这些相似之处表明，这些因素之间可能会发生串扰，其相互作用很可能会改变正常细胞和肿瘤细胞的行为，特别是在肥胖中。了解脂联素和瘦素如何与雄激素受体信号相互作用，可能会指导治疗方法的发展，旨在增强脂联素和雄激素受体的抑制作用或干扰瘦素在BC中的促刺激作用。肥胖是一个日益严重的健康挑战，被认为是乳腺癌的一个危险因素。虽然肥胖相关的乳腺癌机制尚不完全清楚，但这种关联与功能失调的肥胖脂肪组织（增生性和肥厚性脂肪细胞）的激素分泌受损有关。在这些激素中，雄激素和脂肪因子的产生改变被观察到，两者都与乳腺癌的发展独立相关。在这篇综述中，我们描述和评论了这些因素与乳腺癌之间的关系，重点是生物学关联，这些关联有助于揭示雄激素和脂肪因子信号通路改变乳腺上皮细胞行为的机制。此外，我们还讨论了脂肪组织产生的两种最丰富的脂肪因子（脂联素和瘦素）与雄激素受体（乳腺癌的新兴标志物）之间的潜在串扰。研究脂肪因子与雄激素受体在肿瘤细胞中的相互作用，对于指导新的治疗方法的发展，以预防和治疗肥胖和乳腺癌是必要的。
Despite increased information showing obesity is an important breast cancer (BC) risk factor, the mechanisms implicated in this association are not well understood. In this review we describe multiple lines of evidence indicating that altered secretion of androgens and adipokines, from dysfunctional adipose tissue, are independently linked with BC development. However, adipokines (adiponectin and leptin) participate in important biological processes in BC cells by modulating signaling pathways similar to those used by the androgen receptor. These similarities suggest that crosstalk between these factors can occur, with a high probability that its interactions may be responsible for modifying the behavior of normal and tumor cells, especially in obesity. The knowledge of how adiponectin and leptin can interact with the androgen receptor signaling may prospectively guide the development of therapeutic approaches aimed at potentiating the inhibitory actions of adiponectin and androgen receptor or interfering with the pro-stimulatory role of leptin in BC. Obesity is an increasing health challenge and is recognized as a breast cancer risk factor. Although obesity-related breast cancer mechanisms are not fully understood, this association has been linked to impaired hormone secretion by the dysfunctional obese adipose tissue (hyperplasic and hypertrophic adipocytes). Among these hormones, altered production of androgens and adipokines is observed, and both, are independently associated with breast cancer development. In this review, we describe and comment on the relationships reported between these factors and breast cancer, focusing on the biological associations that have helped to unveil the mechanisms by which signaling from androgens and adipokines modifies the behavior of mammary epithelial cells. Furthermore, we discuss the potential crosstalk between the two most abundant adipokines produced by the adipose tissue (adiponectin and leptin) and the androgen receptor, an emerging marker in breast cancer. The identification and understanding of interactions among adipokines and the androgen receptor in cancer cells are necessary to guide the development of new therapeutic approaches in order to prevent and cure obesity and breast cancer.
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影响因子：
11.2
作者：
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通讯作者：
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影响因子：
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