Imtiaz Khalil Research

Although TLKs role in genome maintenance is well-understood, TLKs functionality in other processes of tumorigenesis is yet to be explored. I am currently exploring TLK1’s role in cancer metastasis, especially in prostate cancer (PCa). Prostate tumors can be initially treated by androgen deprivation therapy (ADT), however, within a short period of time, tumors relapses with more aggressive phenotype and start spreading to other organs of the body. Metastatic dissemination of cancer cells is the major cause of PCa related death. ADT increases TLK1B level and we hypothesized that this increase is associated with increased mobility of the PCa cells which may promote PCa metastasis. In fact, we exhibited that TLK1/1B can interact and phosphorylate another promotility factor called MAPK activated protein kinase 5 (MAPKAPK5/MK5/PRAK) and increase its catalytic activity. MK5 is a known promotility factor which can regulate actin polymerization, focal adhesion complex modification, and matrix metalloproteinases (MMPs) expression. We have evidence that TLK1-MK5 signaling is active in majority of the PCa cell lines and disruption of this signaling can reduce migration of both non-malignant and PCa cells. I am currently trying to elucidate the mechanisms of TLK1-MK5 signaling in enhancing PCa cell migration and invasion. In near future, I will also test if inhibition of TLK1-MK5 signaling can reduce metastatic burden of PCa cells in xenograft mice model. Successful completion of these studies may be translated into the application of TLK1-MK5 inhibitors in the treatment of metastatic PCa patients in conjunction with anti-androgen therapies.