Overview
Topic status: We're looking for students to study this topic.
Background: Metastatic spread of cancers is a complicated process that signifies the end stage of many cancers in humans. Understanding the molecular mechanisms of cancer cell motility will improve therapeutic intervention and result in better outcome for patients.
EphB4 is a receptor tyrosine kinase that can have both oncogenic and tumour suppressive functions depending on cell context and ligand-dependent or independent signalling activities. Furthermore, EphB4 has been implicated in cancer cell motility especially in breast and prostate. Src kinase signalling is linked to Pi3K and MAPK signalling pathways, both signalling cascades that are overactive in cancers. Dasatinib is a cytostatic Src kinase inhibitor that shows promising results for treatment of solid tumour such as breast and prostate cancer particularly in patients with advanced metastatic spread to the bone. We have identified several Src kinase family members as possible downstream targets of EphB4. This implicates that EphB4 could promote oncogenic behaviour via Src kinase signalling and that this could be inhibited by dasatinib. We have several cell line models with exogenous or endogenous over-expression of EphB4 that can be used to study the effects of inhibiting EphB4 signalling by dasatinib. This project will explore how EphB4 and Src kinases work together to promote tumourigensis and look at the possibility of dasatinib to perturb this activity.
Further comments:
- Src kinases regulate EphB4 signalling leading to oncogenic behaviour.
- Establish Src kinase family members involved in EphB4 signalling
- Determine if Src kinase inhibition by dasatinib reverses EphB4-mediated tumour promoting behaviour
Approaches:
- Cell culture (human cancer cell lines; prostate and/or breast)
- Cell signalling pathway analysis using immunoblotting
- Cytotoxicity assays
- Apoptosis assays
- Proliferation & cell migration assays
- Study level
- Honours
- Supervisors
- QUT
- Organisational unit
Science and Engineering Faculty
- Research area
- Contact
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Please contact the supervisors.
Dr Inga Mertens-Walker
Dr Sally-Anne Stephenson
Professor Adrian Herington
