Abstract 4906: TLK1-MK5 signaling axis contributes to prostate cancer cell motility and invasion

Background: Prostate cancer (PCa) is the 2nd leading death-causing malignancy in men where the majority of fatalities occur due to metastasis of cancer cells to adjacent and distal organs. We identified the novel interaction between two kinases that may initiate a signaling cascade promoting metastasis. One kinase is MAPK activated protein kinase 5 (MAPKAPK5 or MK5) which plays a debated role in cellular motility along with other cellular processes. Our observations are that MK5 interacts with another S/T kinase, called tousled like kinase 1 (TLK1), which may also have a potential role in cellular motility which is largely unstudied, apart from one report in breast cancer on TLK2. In PCa, TLK1-MK5 signaling axis might be crucial as androgen deprivation therapy leads to increased expression of both TLK1 and MK5 in metastatic castrate-resistant prostate cancer patients. Our working hypothesis is that TLK1-MK5 axis promotes PCa cell motility and invasion through actin rearrangement as well as focal adhesion proteins modification and disruption of this interaction may help to keep the tumor localized. Method and Results: A previous proteomic screening from our lab identified MK5 as one of the novel interactors of TLK1 with high confidence (p Conclusion: Our data support that TLK1-MK5 interaction is functionally involved in cell motility and migration and hence, disruption of this axis may inhibit the metastasis of PCa. Citation Format: Md Imtiaz Khalil, Vibha Singh, Arrigo De Benedetti. TLK1-MK5 signaling axis contributes to prostate cancer cell motility and invasion [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4906.