Targeting the TLK1-MK5 Axis Suppresses Prostate Cancer Metastasis.

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.