Molecular mechanisms of cancer biology: Our lab is interested in molecular mechanisms of cancer biology, particularly concerning members of the Ras superfamily of proteins. Ras proteins are the prototypes for a large superfamily of related small GTPases whose activity is regulated by a cycle of GTP/GDP binding and subcellular localization, and whose diverse functions in cellular physiology include growth, invasion, motility, cell cycle control, differentiation and death. Whereas normal signal transduction by Ras family proteins is required for proper cell growth and differentiation resulting from a wide variety of different inputs, their malfunction or deregulated activity is linked to uncontrolled cell proliferation or inappropriate cell suicide. Indeed, mutated Ras genes are the most commonly mutated oncogenes in human cancer, and their deregulated function as a consequence of alterations in other proteins is also a critical mechanism driving many cancer cells. In our lab, studying the mechanisms whereby mammalian Ras family proteins and their cousins control the conversion of extracellular signals to intracellular responses provides us with several broad areas of experimentation with both basic science and translational bents.
• Location location location: where small GTPases go and why
• Disruption of lipid modifications for cancer treatment
• Ras and Rho family GTPases: why so many?
• Radiation responsiveness: control of death, arrest or survival
Fiordalisi, J.J., Keller, P.J., and Cox, A.D. (2006) PRL tyrosine phosphatases regulate rho family GTPases to promote invasion and motility. Cancer Res 66(6): 3153-61. Abstract
Bivona, T.G., Quatela, S.E., Bodemann, B.O., Ahearn, I.M., Soskis, M.J., Mor, A., Miura, J., Wiener, H.H., Wright, L., Saba, S.G., Yim, D., Fein, A., Perez de Castro, I., Li, C., Thompson, C.B., Cox, A.D., and Philips, M.R. (2006) PKC Regulates a Farnesyl-Electrostatic Switch on K-Ras that Promotes its
Association with Bcl-XL on Mitochondria and Induces Apoptosis. Mol Cell 21(4): 481-93. Abstract
Capell, B.C., Erdos, M.R., Madigan, J.P., Fiordalisi, J.J., Varga, R., Conneely, K.N., Gordon, L.B., Der, C.J., Cox, A.D., and Collins, F.S. (2005) Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A 102(36): 12879-84. Abstract
Keller P.J., Gable C.M., Wing M.R., and Cox A.D. (2005) Rac3-mediated transformation requires multiple effector pathways. Cancer Res 65(21): 9883-90. Abstract
Berzat, A.C., Buss, J.E., Chenette, E.J., Weinbaum, C.A., Shutes, A., Der, C.J., Minden, A., and Cox, A.D. (2005) Transforming activity of the Rho family GTPase, Wrch-1, a Wnt-regulated Cdc42 homolog, is dependent on a novel carboxyl-terminal palmitoylation motif. J Biol Chem 280(38): 33055-65. Abstract
Lim, K.H., Baines, A.T., Fiordalisi, J.J., Shipitsin, M., Feig, L.A., Cox, A.D., Der, C.J., and Counter, C.M. (2005) Activation of RalA is critical for Ras-induced tumorigenesis of human cells. Cancer Cell 7(6): 533-45. Abstract
