Targeting invasion and metastasis


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Margaret Frame

Beatson Institute for Cancer Research, Glasgow, UK

Abstract

Targeting invasion and metastasis

One of the hallmarks of cancer cells is their ability to invade into adjacent tissue and metastasise. We have been studying invasion and metastasis, leading to studies that will take forward development of small molecule inhibitors of invasion for clinical use. Our basic work focuses on the role of the non-receptor tyrosine kinases Src and its substrate focal adhesion kinase (FAK). Src is the prototypical oncogene and we have established that is has an important role in controlling both cadherin-mediated cell-cell contacts and integrin-dependent cell-matrix adhesions, and the crosstalk between these that is perturbed in cancer. Indeed, highly elevated Src activity in rarely required for the proliferation of advanced tumour cells, instead promoting cancer invasion and metastasis by perturbing cancer cell adhesions. We also showed, via conditional deletion of FAK in the skin of mice, that FAK plays a key role in tumour formation and progression. We are now combining new technologies of intra-vital dynamic molecular imaging, and genetically engineered mouse cancer modelling, to address the important question of whether agents that target adhesion regulators have anti-invasive or anti-metastatic activity, and if so how such activity can be monitored. We seek a full understanding of the molecular mechanisms by which these adhesion regulated kinases promote the malignant phenotype.