Objective
Of the protein kinase C (PKC) family of protein kinases, several isoforms including PKCalfa have been implicated in promoting a cell migratory phenotype. In MCF - 7 breast cancer epithelial cells, the signal machinery that drives cell migration towards Beta1 integrin substrates is dependent upon PKCCalfa-catalysed recycling of the activated pool of beta1 integrin receptors. More recently, Dr Ng's group has shown, by fluorescence resonance energy transfer (FRET) measured by fluorescence lifetime imaging microscopy (FLIM) and biochemical analyses, that ezrin (an F-actin-binding protein) interacts with PKCalfa upon activation and is involved in mediating PKC-induced directional cell movement. Also, PKCalfa is the only kinase shown in vivo to be responsible for the phosphorylation and hence activation of ERM (ezrin, radixin, moesin) proteins. The FLIM/FRET imaging approach allows for the first time a "precise" spatiotemporal resolution of biochemical processes in living cells and archived pathological tissues. This study is designed to further characterize the molecular determinants of the PKC-ezrin complex formation. The aim is to understand the mechanisms underpinning breast cancer cell invasion.
Basic studies will be conducted in human metastatic breast cells, which are stimulated to migrate towards a chemotactic factor gradient in the Dunn direct-viewing chamber. The results of these studies will help us to construct and screen retrovirally encoded minigenes, which should disrupt PKCCalfa-ezrin complex formation in order to target carcinoma cells in an athymic nude murine model of metastasis.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology environmental engineering waste management waste treatment processes recycling
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy fluorescence lifetime imaging
- medical and health sciences clinical medicine oncology breast cancer
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
SE1 7EH LONDON
United Kingdom
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