PKN kinases are AGC-type Serine/Threonine kinases. In contrast to other PKN kinases, PKN3 is physiologically expressed mainly in primary endothelial cells and osteoclasts but is also frequently overexpressed in tumor cells. In tumor cells, PKN3 has been shown to act downstream of PI3-kinase activation to promote malignant progression of prostate cancer. Conversely, reduction of PKN3 expression resulted in impaired primary tumor growth and inhibition of metastasis in breast and prostate cancer. Mechanistically, PKN3 is thought to be involved in the regulation of F-actin organization in a RhoA-dependent manner.
The aim of this project will be to analyze the crosstalk of PKN3 and Rho signaling in cancer cells, focusing on their potential synergistic effect on F-actin dynamics and tumor cell motility in both 2D and 3D environments. The project will build up on our recent findings of new potential substrates and binding partners of PKN3. The interaction of PKN3 and its effect on these newly discovered substrates and interactors will be evaluated by biochemical analyses and subsequent cell-based assays in cancer cell line and endothelial cell models.
The PGS candidate should have experience in mammalian cell cultivation techniques, molecular cloning and basic fluorescence microscopy. Experience with live-cell microscopy, and/or CRISPR/Cas9 are of further advantage.
Five relevant publications of the research group: