Research Interests

Signal Transduction Pathways, GTPases and Cell Cycle Control

Small GTPases

The Oncogene Team studies the roles of cell signalling pathways in cancer. 

A major focus is the function of the Ras and Rho families of small GTPases. A particular focus in our current studies is the mechanisms of tumour cell movement underpinning invasion and metastasis of cancer cells. We have found that as well as a previously described Rac driven lamelliopdial form of cell movement, there is an alternative mode of cell movement that unlike Rac driven protrusive movement is absolutely dependent on Rho signalling to Rho kinase. This form of cell movement was only revealed through observing cells moving in three dimensions rather than along a flat surface in standard tissue cultures. 

Strikingly we have been able to show that these two forms of movement have different requirements for extracellular proteoloysis to degrade the extracellular matrix and for Rho GTPase-regulated signalling pathways. Furthermore we have been able to show that the different forms of cell movement are interconvertible, revealing the plasticity of cell movement mechanisms. The mechanisms controlling tumour cell movement are now a central theme of our studies. For example, we are studying how the level of actomyosin contractility determines cell morphology and mode of cell movement, how cells interconvert between modes of movement and how Rho family GTPase signalling determines cell movement. 

In order to understand Ras and Rho family GTPase signalling we are using a combination of tissue culture assays and in vivo experiments using conditional knockouts of signal transduction components in genetically engineered mouse models of human cancer.

External Funding: Cancer Research UK, EU
Investigators: Jessica Ahn, Faraz Khosravi Mardakheh, Sandra Kümper, Valerie Leblanc-Dominguez, Chris Marshall, Afshan McCarthy, Ryan McCully, Hugh Paterson, Pascal Peschard, Amine Sadok, Annette Self, Maggie Yeo.