Pioneer of prostate cancer: past, present and the future of FOXA1.
Pioneer of prostate cancer: past, present and the future of FOXA1.
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DOI：
10.1007/s13238-020-00786-8
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发表时间：
2021-01
期刊：
影响因子：
21.1
通讯作者：
He HH
中科院分区：
文献类型：
--
作者：
Teng M;Zhou S;Cai C;Lupien M;He HH
前列腺癌是北美男性中最常见的非皮肤癌症。虽然雄激素剥夺一直是前列腺癌治疗的基石，但随之而来的耐药性导致了致命的疾病。叉头盒A1 （FOXA1）编码一个先导因子，该因子诱导开放染色质构象，从而允许其他转录因子结合。通过与雄激素受体（AR）的直接相互作用，FOXA1帮助形成驱动正常前列腺和前列腺癌细胞生长和存活的AR信号。FOXA1还具有不依赖ar的调节上皮-间质转化（EMT）的作用。在前列腺癌中，突变集中在FOXA1的编码序列和顺式调控元件（CREs）上，导致功能改变。此外，前列腺癌中FOXA1的活性可通过多种机制进行翻译后调节，如lsd1介导的蛋白去甲基化。在这篇综述中，我们描述了FOXA1在前列腺癌中的功能和调控的最新发现，指出它们与指导未来临床干预的相关性。
Prostate cancer is the most commonly diagnosed non-cutaneous cancers in North American men. While androgen deprivation has remained as the cornerstone of prostate cancer treatment, resistance ensues leading to lethal disease. Forkhead box A1 (FOXA1) encodes a pioneer factor that induces open chromatin conformation to allow the binding of other transcription factors. Through direct interactions with the Androgen Receptor (AR), FOXA1 helps to shape AR signaling that drives the growth and survival of normal prostate and prostate cancer cells. FOXA1 also possesses an AR-independent role of regulating epithelial-to-mesenchymal transition (EMT). In prostate cancer, mutations converge onto the coding sequence and cis-regulatory elements (CREs) of FOXA1, leading to functional alterations. In addition, FOXA1 activity in prostate cancer can be modulated post-translationally through various mechanisms such as LSD1-mediated protein demethylation. In this review, we describe the latest discoveries related to the function and regulation of FOXA1 in prostate cancer, pointing to their relevance to guide future clinical interventions.
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