Olatunde Damilola, Franco Omar Coronel, Gaestel Matthias, De Benedetti Arrigo
Department of Biochemistry and Molecular Biology, Louisiana State University Health Shreveport, Shreveport, LA 71103, USA.
Institute of Cell Biochemistry, Hannover Medical School, 30625 Hannover, Germany.
Cancers (Basel). 2025 Mar 31;17(7):1187. doi: 10.3390/cancers17071187.
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. In this study, we directly examined the effects of disrupting the TLK1>MK5 axis on the motility, invasiveness, and metastatic potential of PCa cells. To establish this, we used both pharmacologic and systemic approaches with genetically engineered mouse models and the use of IVIS. 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.
转移性前列腺癌（PCa）的扩散是导致大多数PCa相关死亡的原因，然而驱动这一过程的精确机制仍不清楚。我们发现了两种不同的促迁移因子——凌乱样激酶1（TLK1）和丝裂原活化蛋白激酶激活的蛋白激酶5（MK5）之间的一种新相互作用，这种相互作用触发了一个促进转移的信号级联反应。在前列腺癌中，TLK1-MK5通路可能起关键作用，因为雄激素剥夺疗法（ADT）与转移性患者中TLK1和MK5的表达增加有关，而这些患者的生存率较低。在本研究中，我们直接研究了破坏TLK1>MK5轴对前列腺癌细胞的迁移、侵袭和转移潜能的影响。为了证实这一点，我们对基因工程小鼠模型同时采用了药理学和全身方法，并使用了IVIS。靶向TLK1>MK5轴的结果支持了这样一种观点，即该轴对于转移细胞的扩散和与年龄相关的转移的发展至关重要。
