Androgen receptor on the move: boarding the microtubule expressway to the nucleus.
Androgen receptor on the move: boarding the microtubule expressway to the nucleus.
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DOI：
10.1158/0008-5472.can-12-0783
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发表时间：
2012-09-15
期刊：
影响因子：
11.2
通讯作者：
Giannakakou P
中科院分区：
文献类型：
--
作者：
Thadani-Mulero M;Nanus DM;Giannakakou P
最近的研究表明，通常用于治疗前列腺癌的微管稳定药物紫杉醇通过抑制雄激素受体（AR）在微管稳定下游的核积累来抑制其信号传导。该机制独立于紫杉醇诱导的有丝分裂停止，可能提供一种替代的药物作用机制，可以解释其临床活性。在这篇综述中，我们强调了依赖于完整和动态微管的信号传导和运输途径的重要性，因此它们代表了微管抑制剂的下游靶点。我们展示了前列腺癌，这是由雄激素受体（AR）的活性驱动的，因为最近的报道揭示了AR的微管依赖性运输与紫杉烷的临床疗效之间的联系。鉴定和进一步阐明微管依赖的肿瘤特异性途径将有助于我们更好地了解临床紫杉烷耐药的分子基础，以及识别更有可能对治疗有反应的个体患者。
Recent studies have shown that the microtubule-stabilizing drug, paclitaxel, which is commonly used for the treatment of prostate cancer inhibits signaling from the androgen receptor (AR) by inhibiting its nuclear accumulation downstream of microtubule stabilization. This mechanism is independent of paclitaxel-induced mitotic arrest and could provide an alternative mechanism of drug action that can explain its clinical activity. In this review, we highlight the importance of signaling and trafficking pathways that depend on intact and dynamic microtubules and as such they represent downstream targets of microtubule inhibitors. We showcase prostate cancer, which is driven by the activity of the androgen receptor (AR), as recent reports have revealed a connection between the microtubule-dependent trafficking of AR and the clinical efficacy of taxanes. Identification and further elucidation of microtubule-dependent tumor-specific pathways will help us better understand the molecular basis of clinical taxane resistance as well as identify individual patients more likely to respond to treatment.