文章：

靶向TLK1-MK5轴可抑制前列腺癌转移

Targeting the TLK1-MK5 Axis Suppresses Prostate Cancer Metastasis

原文发布日期：31 March 2025

DOI: 10.3390/cancers17071187

类型: Article

开放获取: 是

英文摘要：

Background:The spread of metastatic prostate cancer (PCa) is responsible for the majority of PCa-related deaths, yet the precise mechanisms driving this process remain unclear. We have identified a novel interaction between two distinct promotility factors, tousled-like kinase 1 (TLK1) and MAPK-activated protein kinase 5 (MK5), which triggers a signaling cascade that promotes metastasis. In PCa, the TLK1-MK5 pathway may play a critical role, as androgen deprivation therapy (ADT) has been linked to increased expression of both TLK1 and MK5 in metastatic patients linked with poor survival.Objectives:In this study, we directly examined the effects of disrupting the TLK1>MK5 axis on the motility, invasiveness, and metastatic potential of PCa cells.Methods:To establish this, we used both pharmacologic and systemic approaches with genetically engineered mouse models and the use of IVIS.Results:The results of targeting the TLK1>MK5 axis support the notion that this axis is essential for the spread of metastatic cells and the development of age-related metastases.

摘要翻译： 

背景：转移性前列腺癌（PCa）的扩散是导致大多数PCa相关死亡的主要原因，然而驱动这一过程的确切机制尚不明确。我们发现两种不同的促运动因子——tousled样激酶1（TLK1）与MAPK激活蛋白激酶5（MK5）之间存在新型相互作用，这种作用会触发促进转移的信号级联反应。在前列腺癌中，TLK1-MK5通路可能发挥关键作用，因为雄激素剥夺疗法（ADT）与转移患者体内TLK1和MK5表达增加相关，且此类患者生存预后较差。 目的：本研究直接检测了阻断TLK1>MK5轴对前列腺癌细胞运动能力、侵袭性和转移潜能的影响。 方法：为验证这一机制，我们采用药理学和系统生物学方法，结合基因工程小鼠模型及活体成像系统（IVIS）进行研究。 结果：靶向TLK1>MK5轴的研究结果支持以下观点：该轴对转移性细胞的扩散及年龄相关性转移灶的形成具有重要作用。

原文链接：

Targeting the TLK1-MK5 Axis Suppresses Prostate Cancer Metastasis