TLK1‐MK5 Axis Modulates Actin Filaments and Focal Adhesion Components to Promote PCa Cell Migration and Invasion

Metastatic dissemination of prostate cancer (PCa) accounts for majority of PCa related deaths. However, the exact mechanism of PCa cell spread is still unknown. We uncovered a novel interaction between two unrelated promotility factors, tousled‐like kinase 1 (TLK1) and MAPK‐activated protein kinase 5 (MK5), which initiates a signaling cascade promoting metastasis. In PCa, TLK1‐MK5 signaling might be crucial as androgen deprivation therapy (ADT) leads to increased expression of both TLK1 and MK5 in metastatic patients. Moreover, TCGA analysis also revealed higher expression of both TLK1 and MK5 in metastatic tumors. Therefore, we hypothesize that TLK1‐MK5 axis promotes PCa cell migration and invasion through actin reorganization as well as focal adhesion proteins modification and disruption of this interaction may help to keep the tumor localized.