Cancer chemotherapeutic drugs such as taxol (paclitaxel) and vinca alkaloids target dividing cells by interfering with the function of the mitotic spindle, thereby inhibiting cell proliferation and inducing cell death by the process of apoptosis. These drugs are often effective in treating cancers but their use is limited by toxic side effects and the development of resistance. In order to improve their use, we need to understand the mechanisms that determine how cancer cells react to these drugs.
p68 (DDX5) is a prototypic member of the DEAD box family of RNA helicases that can unwind RNA in a context-selective and ATP-dependent manner. p68 is a multi-functional protein known to be involved in several cellular processes requiring manipulation of RNA structures, including transcription and processing of pre-mRNA, rRNA, and miRNA.
Post-translational modifications (PTMs) are chemical modifications that play a key role in protein regulation, as they can regulate activity, localization and interaction with other proteins, or DNA. The relevance of PTMs in cancer development is well established.
Growth factors (e.g. EGF, FGF, PDGF, VEGF) and associated receptor tyrosine kinases (RTKs) regulate key signal transduction pathways which are frequently dysregulated in cancer. RTK pathways are common targets in chemotherapy drug development, but optimal patient selection and drug efficacy is often limited by lack of target specificity.
Colorectal cancer, one of the most common cancers in the UK, is treated by a multi-disciplinary team, combining expertise in surgery, chemotherapy and radiotherapy.
Background and Aims: Cells need to migrate away from their microenvironment to enable the tumour to metastasise. The growth factors Epidermal Growth Factor (EGF) and Transforming Growth Factor α (TGFα) stimulate the migration of fibroblasts into 3D collagen gels. Experiments using a number of growth factors concluded that some stimulated Akt phosphorylation whilst others reduced the phosphorylation of this pathway, but all stimulated migration; suggesting that multiple pathways are important for cell motility.
Project Background: The growth factor VEGF and a signal transduction pathway protein, Akt, may have an important role in oral tumours. Oral cancer patients from Dundee have been shown to have an increased expression of VEGF both in their tissue and in their serum. It has also been reported that Akt is activated in response to growth factors and this activation may be blocked by inhibitors.
Signalling through the classical Ras/ERK MAP kinase pathway is implicated in the genesis and progression of human tumours carrying activating mutations is upstream pathway effectors such as receptor tyrosine kinases and the Ras family of cellular proto-oncogenes.
Background: Two principle surveillance mechanisms have evolved to guard against errors during chromosome segregation. The mitotic checkpoint delays mitosis until each and every sister chromatid has achieved stable attachment to spindle microtubules (via a protein complex known as the kinetochore), and the microtubule error-correction pathway guides this attachment process by ensuring it remains free of errors. In spite of these safeguards, the majority of tumours still manage to continually missegregate their genome.