University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh bioQuarter, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Institute for Regeneration and Repair, University of Edinburgh, Edinburgh bioQuarter, 5 Little France Drive, Edinburgh EH16 4UU, UK.
Cells. 2019 Apr 23;8(4):370. doi: 10.3390/cells8040370.
Despite recent efforts, prostate cancer (PCa) remains one of the most common cancers in men. Currently, there is no effective treatment for castration-resistant prostate cancer (CRPC). There is, therefore, an urgent need to identify new therapeutic targets. The Hippo pathway and its downstream effectors-the transcriptional co-activators, Yes-associated protein (YAP) and its paralog, transcriptional co-activator with PDZ-binding motif (TAZ)-are foremost regulators of stem cells and cancer biology. Defective Hippo pathway signaling and YAP/TAZ hyperactivation are common across various cancers. Here, we draw on insights learned from other types of cancers and review the latest advances linking the Hippo pathway and YAP/TAZ to PCa onset and progression. We examine the regulatory interaction between Hippo-YAP/TAZ and the androgen receptor (AR), as main regulators of PCa development, and how uncontrolled expression of YAP/TAZ drives castration resistance by inducing cellular stemness. Finally, we survey the potential therapeutic targeting of the Hippo pathway and YAP/TAZ to overcome PCa.
尽管最近做了很多努力，前列腺癌（PCa）仍然是男性中最常见的癌症之一。目前，对于去势抵抗性前列腺癌（CRPC）还没有有效的治疗方法。因此，迫切需要确定新的治疗靶点。 Hippo 通路及其下游效应物——转录共激活因子 Yes 相关蛋白（YAP）及其同源物，PDZ 结合基序的转录共激活因子（TAZ）——是干细胞和癌症生物学的主要调节因子。Hippo 通路信号的缺陷和 YAP/TAZ 的过度激活在各种癌症中都很常见。在这里，我们借鉴了其他类型癌症的研究成果，综述了 Hippo 通路和 YAP/TAZ 与前列腺癌发生和进展相关的最新进展。我们研究了 Hippo-YAP/TAZ 与雄激素受体（AR）之间的调控相互作用，AR 是前列腺癌发展的主要调节因子，以及 YAP/TAZ 的不受控制表达如何通过诱导细胞干性来导致去势抵抗。最后，我们调查了 Hippo 通路和 YAP/TAZ 的潜在治疗靶点，以克服前列腺癌。
Zotero 插件
