Professor Anne Ridley
WELCOME TO THE RIDLEY CELL SIGNALLING IN MIGRATION LABORATORY
The Ridley group study how cell migration contributes to cancer progression. In cancer, cell migration underlies the invasion and metastasis of tumour cells, as well as immune response to tumours. Our research focuses on Rho family GTPases, which coordinate cell migration by driving cytoskeletal and cell adhesion dynamics. We aim to identify proteins that could be targeted therapeutically to treat cancer.
Cancer metastasis is associated with poor prognosis and is difficult to treat. Cancer cells in tumours often become motile, invading surrounding tissues, and eventually spreading to other sites in the body via the bloodstream. We and others have shown that Rho GTPases coordinate cell migration through their effects on the cytoskeleton and cell adhesion, and hence contribute to cancer progression and metastasis.
Rho GTPase activity in cells is regulated by a variety of extracellular and intracellular stimuli, and when Rho GTPases are activated, they act through multiple downstream targets to regulated cell migration. We postulate that targeting Rho GTPase signalling networks could provide a route to develop new therapies to reduce cancer progression.
One of the steps in metastasis is the attachment of circulating cancer cells to endothelial cells lining the bloodstream. Our research shows that inhibiting this attachment can reduce metastasis in model systems, and hence we aim to identify the molecular basis for cancer cell: endothelial cell interaction.
We aim to identify molecules that play a central role in cancer progression and metastasis, with the goal to inform the development of new therapies to treat cancer patients in the future.
Our group uses several complementary model systems to study cell migration. We use human cancer cells, including prostate and breast cancer cell lines, B-cell and T-cell leukaemia cells, and non-cancer ‘stromal’ cells that are present in tumours, such as endothelial cells. We combine a variety of approaches and technologies, including cell and molecular biology, RNAi screening, 2D and 3D models for cancer migration and invasion in vitro, live cell imaging by time-lapse microscopy, and in vivo analysis of cancer cells and endothelial cells.
We are currently investigating the molecular basis for cancer progression in several complementary projects:
1) Transmigration of cancer cells across endothelial cells. We have carried out RNAi screens to identify several Rho GTPases and some of their downstream targets that mediate attachment of prostate and breast cancer cells to endothelial cells, and subsequent transmigration across endothelial cells. We are now studying how these different proteins contribute to cancer cell: endothelial cell interaction.
2) Epithelial cancer cell migration and invasion. We recently used RNAi screening to identify Rho GTPase signalling components that regulate prostate cancer cell migration and invasion. We are following up on hits from these screens, including the little-studied RhoH protein, which is unexpectedly expressed in a variety of epithelial tumours and cancer cell lines.
3) Leukaemia cell adhesion and migration. Following on our earlier work identifying a role of the Rho GTPase RhoU in T-acute lymphoblastic leukaemia (T-ALL), we are investigating how RhoU and its relative RhoV act at a molecular level to regulate T-ALL and other types of cancer cell adhesion and migration. In addition, we are investigating how the transmembrane enzyme CD38 contributes to B-cell chronic lymphocytic leukaemia (CLL) progression through acting on the small GTPase Rap1 to promote CLL cell adhesion and migration.
Qualifications for Professor Anne Ridley
- 1989: PhD University of London
- 1989-90: EMBO postdoctoral fellow, Whitehead Institute, Cambridge, USA
- 1990-93: Postdoctoral fellow, Institute of Cancer Research, London, UK
- 1993-2007: Group leader, Ludwig Institute of Cancer Research, London, UK
- 2003-07: Professor of Cell Biology, University College London, UK
- 2007-17: Professor of Cell Biology, King’s College London, UK
- 2018- : Head of School of Cellular and Molecular Medicine, University of Bristol, UK
- 2000: Hooke Medal, British Society of Cell Biology
- 2002: Member, EMBO
- 2004: Lilian-Bettencourt Prize for the Life Sciences
- 2009: Fellow of Society of Biology
- 2012: Fellow of Academy of Medical Sciences
- 2014: Honorary Fellow of Royal Microscopical Society
- 2017: Fellow of Royal Society
- Tajadura, V., Garg, R., Allen, R., Owczarek, C., Bright, M.D., Kean, S., Mohd-Noor, A.,, Grigoriadis, A., Elston, T.C., Hahn, K.M., Ridley, A.J. (2018) An RNAi screen of Rho signaling networks identifies RhoH as a regulator of Rac1 in prostate cancer cell migration. BMC Biol. 16, 29.
- Mele, S., Devereux, S., Pepper, A.G., Infante, E., Ridley, A.J. (2018) Calcium-RasGRP2-Rap1 signaling mediates CD38-induced migration of chronic lymphocytic leukemia cells. Blood Advances 2,1551-1561.
- McColl, B., Garg, R., Riou, P., Riento, K., Ridley, A.J. (2016). Rnd3-induced cell rounding requires interaction with Plexin-B2. J. Cell Sci 129, 4046-4056.
- Bhavsar, P.J., Infante, E., Khwaja, A., Ridley, A.J. (2013) Analysis of Rho GTPase expression in T-ALL identifies RhoU as a target for Notch involved in T-ALL cell migration. Oncogene 32, 198-208.
- Reymond, N., Im, J.H., Garg, R., Vega, F.M., Borda d’Agua, B., Riou, P., Cox, S., Valderrama, F., Muschel, R.J., Ridley, A.J. (2012) Cdc42 promotes transendothelial migration of cancer cells through β1 integrin. J. Cell Biol. 199, 653-668.
Cancer Research UK, Worldwide Cancer Research, MRC, BBSRC.