Dipartimento di Scienze del Farmaco, Università Degli Studi di Pavia, Viale Taramelli 12/14, 27100 Pavia, Italy.
Scuola Universitaria Superiore IUSS, Piazza della Vittoria 15, 27100 Pavia, Italy.
Cells. 2021 Nov 3;10(11):2999. doi: 10.3390/cells10112999.
Cancer is one of the most common causes of death worldwide, and its development is a result of the complex interaction of genetic factors, environmental cues, and aging. Hormone-sensitive cancers depend on the action of one or more hormones for their development and progression. Sex steroids and corticosteroids can regulate different physiological functions, including metabolism, growth, and proliferation, through their interaction with specific nuclear receptors, that can transcriptionally regulate target genes via their genomic actions. Therefore, interference with hormones' activities, e.g., deregulation of their production and downstream pathways or the exposition to exogenous hormone-active substances such as endocrine-disrupting chemicals (EDCs), can affect the regulation of their correlated pathways and trigger the neoplastic transformation. Although nuclear receptors account for most hormone-related biologic effects and their slow genomic responses are well-studied, less-known membrane receptors are emerging for their ability to mediate steroid hormones effects through the activation of rapid non-genomic responses also involved in the development of hormone-sensitive cancers. This review aims to collect pre-clinical and clinical data on these extranuclear receptors not only to draw attention to their emerging role in cancer development and progression but also to highlight their dual role as tumor microenvironment players and potential candidate drug targets.
癌症是全球最常见的死亡原因之一，其发展是遗传因素、环境线索和衰老复杂相互作用的结果。激素敏感型癌症的发生和发展依赖于一种或多种激素的作用。性激素和皮质类固醇可以通过与特定核受体的相互作用来调节不同的生理功能，包括代谢、生长和增殖，这些核受体可以通过其基因组作用转录调控靶基因。因此，干扰激素的活性，例如，其产生和下游途径的失调或暴露于外源性激素活性物质（如内分泌干扰化学物质（EDCs）），会影响相关途径的调节，并引发肿瘤转化。尽管核受体占大多数激素相关的生物学效应，其缓慢的基因组反应已经得到很好的研究，但越来越多的未知膜受体因其能够通过激活快速非基因组反应来介导类固醇激素的作用而受到关注，这些快速非基因组反应也参与了激素敏感型癌症的发生。本综述旨在收集这些核外受体的临床前和临床数据，不仅要引起人们对其在癌症发生和发展中的新兴作用的关注，还要强调它们作为肿瘤微环境参与者和潜在候选药物靶点的双重作用。
