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单胺氧化酶 A(MAOA):前列腺癌治疗的有前途的靶点。

Monoamine oxidase A (MAOA): A promising target for prostate cancer therapy.

机构信息

Division of Cancer Biology, Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; School of Basic Medical Sciences, Medical College of Yan'an University, 580 Bao-Ta Street, Yan'an, Shaanxi, 716000, China.

Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, 730030, China.

出版信息

Cancer Lett. 2023 Jun 1;563:216188. doi: 10.1016/j.canlet.2023.216188. Epub 2023 Apr 17.

Abstract

Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes the oxidative deamination of monoamine neurotransmitters and dietary amines. Previous studies have shown that MAOA is clinically associated with prostate cancer (PCa) progression and plays a key role in almost each stage of PCa, including castrate-resistant prostate cancer, neuroendocrine prostate cancer, metastasis, drug resistance, stemness, and perineural invasion. Moreover, MAOA expression is upregulated not only in cancer cells but also in stromal cells, intratumoral T cells, and tumor-associated macrophages; thus, targeting MAOA can be a multi-pronged approach to disrupt tumor promoting interactions between PCa cells and tumor microenvironment. Furthermore, targeting MAOA can disrupt the crosstalk between MAOA and the androgen receptor (AR) to restore enzalutamide sensitivity, blocks glucocorticoid receptor (GR)- and AR-dependent PCa cell growth, and is a potential strategy for immune checkpoint inhibition, thereby alleviating immune suppression and enhancing T cell immunity-based cancer immunotherapy. MAOA is a promising target for PCa therapy, which deserves further exploration in preclinical and clinical settings.

摘要

单胺氧化酶 A(MAOA)是一种线粒体酶,可催化单胺神经递质和膳食胺的氧化脱氨。先前的研究表明,MAOA 与前列腺癌(PCa)的进展临床相关,并在 PCa 的几乎每个阶段都发挥关键作用,包括去势抵抗性前列腺癌、神经内分泌前列腺癌、转移、耐药性、干性和神经周围浸润。此外,MAOA 的表达不仅在癌细胞中上调,而且在基质细胞、肿瘤内 T 细胞和肿瘤相关巨噬细胞中上调;因此,靶向 MAOA 可能是一种多管齐下的方法,可以破坏 PCa 细胞与肿瘤微环境之间促进肿瘤的相互作用。此外,靶向 MAOA 可以破坏 MAOA 和雄激素受体(AR)之间的串扰,从而恢复恩扎卢胺的敏感性,阻断糖皮质激素受体(GR)和 AR 依赖性 PCa 细胞的生长,并且是免疫检查点抑制的潜在策略,从而减轻免疫抑制并增强基于 T 细胞免疫的癌症免疫疗法。MAOA 是 PCa 治疗的一个有前途的靶点,值得在临床前和临床环境中进一步探索。

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