Polo-like kinase 4 (Plk4) has been identified as a molecular marker of resistance to therapy in cancer. Our laboratory has recently shown a motility defect in Plk4+/- murine embryonic fibroblasts (MEFs) compared to Plk4+/+. I hypothesized that Plk4 augments cancer cell motility. Plk4 depletion with siRNA in Plk4+/+ MEFs and HeLa cells suppressed invasion compared to control. Transient over-expression of Flag-Plk4 in cancer cell lines did not consistently increase invasion. However, modest Plk4 over-expression using stable clones showed higher invasion rates than non-induced. The RhoGEF Ect2, an important Plk4 substrate, transiently localized to protrusions in MEFs, suggesting a RhoA-based signalling cascade in motility. The effect of Plk4 heterozygosity on metastasis was tested in a transgenic mouse model but there was no significant difference in developing metastasis compared to wild type. Further studies are required to characterize the effect of Plk4 on motility, and its potential as a therapeutic cancer target.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32295 |
| Date | 26 March 2012 |
| Creators | Zih, Si Wai |
| Contributors | Swallow, Carol |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.0021 seconds