Oncogene:TXNDC9能够调控氧化应激诱导的雄激素受体信号来促进前列腺癌恶化

2019-09-15 AlexYang MedSci原创

活性氧(ROS)和ROS诱导的氧化应激与前列腺癌(PCa)发展和肿瘤去势抵抗性的恶化相关。该过程部分的是通过雄激素受体(AR)信号的激活。然而,ROS激活AR的潜在机制仍旧不清楚。最近,有研究人员报道了包含硫氧还蛋白结构域蛋白9(TXNDC9)是ROS激活AR信号的一个重要的调节因子。TXNDC9的表达可以由ROS诱导上调,TXNDC9表达的上调与晚期临床阶段有关。TXNDC9还能促进PCa细胞生

活性氧(ROS)和ROS诱导的氧化应激与前列腺癌(PCa)发展和肿瘤去势抵抗性的恶化相关。该过程部分的是通过雄激素受体(AR)信号的激活。然而,ROS激活AR的潜在机制仍旧不清楚。

最近,有研究人员报道了包含硫氧还蛋白结构域蛋白9(TXNDC9)是ROS激活AR信号的一个重要的调节因子。TXNDC9的表达可以由ROS诱导上调,TXNDC9表达的上调与晚期临床阶段有关。TXNDC9还能促进PCa细胞生存和增殖。在氧化应激条件下,AR蛋白的表达和AR转录活性是需要的。同样的,ROS诱导因子还能够促进TXNDC9与PRDX1分离,但能够增强与MDM2的联系。这些蛋白互作的改变不仅能勾到熬制MDM2蛋白的降解,还能够促进PRDX1蛋白调节的AR蛋白的稳定,并随后增强AR信号。通过CoA阻断PRDX1能够抑制AR信号、PCa细胞增殖和异种种植肿瘤的生长,甚至是在雄激素阻断条件下。当恩杂鲁胺治疗结合时,CoA的这些肿瘤抑制效果能够得到增强。

最后,研究人员指出,他们的研究阐释了TXNDC9-PRDX1在ROS激活的AR功能中具有重要角色,为共同靶向AR和PRDX1能够更有效的控制PCa生长提供了原理论证。

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    2020-05-20 cy0324
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    2019-09-17 zsyan
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    2019-09-15 misszhang

    前列腺癌相关研究,学习了,谢谢梅斯

    0

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