Master of Science
Stephen H Pasternak
Metastasis is the primary cause of mortality in cancer patients. Inhibition of proteins that are involved in the regulation of metastasis are expected to suppress metastasis and represent treatment targets. Our focus is on prostate cancer metastasis and we have developed a novel high-throughput means of performing in vitro screens for regulators of prostate cancer metastasis. We propose to use a focused CRISPR library screen that will “knock out” all human kinases to determine which ones are responsible for prostate cancer metastasis. CRISPR is a potent genetic editing tool and was used to silence all kinases in prostate cells (BPH cells). These cells form spheroid colonies in 3D culture and were subjected to a CRISPR kinase screen. We observed a morphological change in some colonies to a stellate morphology, which represents aggressive behavior. These stellate colonies were then isolated to identify the responsible kinase. We identified Glycogen synthase kinase 3 beta (GSK3ß) as a potential regulator for prostate cancer cell morphology and possible, metastasis.
Aldhafeeri, Hamad, "CRISPR Screen for Identification of Kinases that Mediate Prostate Cancer Cell Invasion" (2017). Electronic Thesis and Dissertation Repository. 5205.