Dipartimento di Scienze del Farmaco, Università Degli Studi di Pavia, Viale Taramelli 12/14, 27100 Pavia, Italy.
Classe di Scienze Umane e della Vita (SUV), Scuola Universitaria Superiore IUSS, Piazza della Vittoria 15, 27100 Pavia, Italy.
Int J Mol Sci. 2020 Dec 3;21(23):9229. doi: 10.3390/ijms21239229.
Endocrine disruptors (EDCs) can display estrogenic and androgenic effects, and their exposure has been linked to increased cancer risk. EDCs have been shown to directly affect cancer cell regulation and progression, but their influence on tumour microenvironment is still not completely elucidated. In this context, the signalling hub protein RACK1 (Receptor for Activated C Kinase 1) could represent a nexus between cancer and the immune system due to its roles in cancer progression and innate immune activation. Since RACK1 is a relevant EDCs target that responds to steroid-active compounds, it could be considered a molecular bridge between the endocrine-regulated tumour microenvironment and the innate immune system. We provide an analysis of immunomodulatory and cancer-promoting effects of different EDCs in shaping tumour microenvironment, with a final focus on the scaffold protein RACK1 as a pivotal molecular player due to its dual role in immune and cancer contexts.
内分泌干扰物（EDCs）可表现出雌激素和雄激素的作用，其暴露与癌症风险增加有关。EDCs 已被证明可直接影响癌细胞的调控和进展，但它们对肿瘤微环境的影响仍不完全清楚。在这种情况下，信号枢纽蛋白 RACK1（激活蛋白激酶 C 的受体 1）由于其在癌症进展和固有免疫激活中的作用，可能成为癌症和免疫系统之间的联系。由于 RACK1 是一个与甾体活性化合物反应的相关 EDCs 靶标，因此它可以被认为是内分泌调节的肿瘤微环境与固有免疫系统之间的分子桥梁。我们分析了不同 EDCs 在塑造肿瘤微环境方面的免疫调节和促进癌症的作用，最后聚焦于支架蛋白 RACK1，因为它在免疫和癌症环境中具有双重作用，是一个关键的分子参与者。
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