Margaret Frame’s long-held research interests are in cancer invasion and metastasis, and the role of tyrosine kinases in controlling tumour cell spread. She has had several CR-UK funded programs of research to work on understanding cancer invasion and metastasis and was awarded a
European Research Council Advanced Investigator grant to build a novel cancer discovery platform. Her main goal is to work with clinicians treating cancers of unmet need, to determine whether targeting the invasive and metastatic processes may be of therapeutic benefit, and may be monitored in the preclinical and clinical settings by novel imaging techniques. Her group has shown that the FERM domain of FAK interacts with key regulators of directional migration and cancer cell polarity, and that tumour progression requires FAK in multiple epithelial cancer types. They have also demonstrated that Src inhibition suppresses metastasis in a genetically engineered mouse model of
pancreatic cancer, and have been able to generate extremely useful cells from cancer models that are FAK deficient, and which can be reconstituted with wild-type FAK or signalling mutants. These have allowed the group to determine the role of signalling through FAK, from integrins and from the upstream Src kinases, and via FAK’s kinase activity, in maintaining aspects of the cancer phenotype. These have led to several findings on control of E-cadherin dynamics in vitro and in vivo, and on proliferation in 3-dimensional environments. Perhaps the most striking new finding from their genetic deletion studies (in both cells and animal tissues), has been that integrin signalling through the Src/FAK axis regulates autophagy in advanced cancer cells. Margaret Frame's research group is now working with Professor Valerie Brunton, extending her research into
glioblastoma to find out how these same networks are involved in this complex disease. A major part involves studying glioblastoma stem cells looking for differences in their adhesion networks, how these may play a role in the disease and how glioblastoma stem cells interact with immune cells and influence their surroundings. Through this work, they also hope to reveal new drug targets. == Awards and honours ==