Overview
Topic status: We're looking for students to study this topic.
The receptor tyrosine kinase EphB4 is increased on the surface of cancer cells and has been shown to contribute to tumour development by promoting angiogenesis, increasing cancer cell survival, and facilitating invasion and migration. Recently we identified EphB4 as a substrate of the KLK4 serine protease, a protein whose function has been linked to prostate cancer. Protease degradation of Eph receptors and ephrin ligands has been implicated in the regulation of signalling outcomes and this project will determine whether KLK4 regulated the events and outcomes of EphB4-ephrinB2 signalling in prostate cancer.
Hypothesis: KLK4, over-expressed and secreted from prostate cancer cells degrades surface EphB4 and/or ephrinB2, preventing EphB4-ephrinB2 interaction and activation of signalling pathways that normally suppress tumour formation, and thereby facilitating cancer progression.
Aim 1: Determine whether KLK4 can cleave EphB4 and ephrinB2 from the surface of
prostate cancer cells
Aim 2: Determine whether KLK4 can cleave EphB4 and ephrinB2 when the proteins are
interacting in vitro
Aim 3: Determine whether KLK4 cleaved EphB4 and ephrinB2 proteins are still functional signalling molecules by investigating downstream cellular functions such as cell growth and migration
Methods and techniques that will be developed in the course of this project:
- Recombinant protein production and purification
- Cell culture (cancer cells)
- ELISA
- Confocal microscopy
- Western blotting and immunoprecipitation
- Cell proliferation and migration assays
- Study level
- Honours
- Supervisors
- QUT
- Organisational unit
Science and Engineering Faculty
- Research area
- Contact
- Please contact the supervisor.
Dr Sally-Anne Stephenson
Professor Adrian Herington
