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环境暴露与芳香烃受体在乳腺癌肿瘤微环境中的作用

Environmental exposure and the role of AhR in the tumor microenvironment of breast cancer.

作者信息

Sweeney Colleen, Lazennec Gwendal, Vogel Christoph F A

机构信息

Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA, United States.

Centre National de la Recherche Scientifique, SYS2DIAG-ALCEN, Cap Delta, Montpellier, France.

出版信息

Front Pharmacol. 2022 Dec 15;13:1095289. doi: 10.3389/fphar.2022.1095289. eCollection 2022.

Abstract

Activation of the aryl hydrocarbon receptor (AhR) through environmental exposure to chemicals including polycyclic aromatic hydrocarbons (PAHs) and polychlorinated dibenzo-p-dioxins (PCDDs) can lead to severe adverse health effects and increase the risk of breast cancer. This review considers several mechanisms which link the tumor promoting effects of environmental pollutants with the AhR signaling pathway, contributing to the development and progression of breast cancer. We explore AhR's function in shaping the tumor microenvironment, modifying immune tolerance, and regulating cancer stemness, driving breast cancer chemoresistance and metastasis. The complexity of AhR, with evidence for both oncogenic and tumor suppressor roles is discussed. We propose that AhR functions as a "molecular bridge", linking disproportionate toxin exposure and policies which underlie environmental injustice with tumor cell behaviors which drive poor patient outcomes.

摘要

通过环境暴露于包括多环芳烃(PAHs)和多氯二苯并对二恶英(PCDDs)在内的化学物质而激活芳烃受体(AhR),可导致严重的不良健康影响,并增加患乳腺癌的风险。本综述探讨了几种将环境污染物的促肿瘤作用与AhR信号通路联系起来的机制,这些机制有助于乳腺癌的发生和发展。我们研究了AhR在塑造肿瘤微环境、改变免疫耐受和调节癌症干性、推动乳腺癌化疗耐药性和转移方面的功能。文中讨论了AhR的复杂性,有证据表明它兼具致癌和肿瘤抑制作用。我们提出,AhR作为一座“分子桥梁”,将不成比例的毒素暴露以及构成环境不公正基础的政策与导致患者预后不良的肿瘤细胞行为联系起来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ccc/9797527/589359f4c6bb/fphar-13-1095289-g001.jpg

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