University of Cincinnati, B.S. Chemistry/Biochemistry, 1986;
University of Kentucky, Ph.D., Biochemistry, 1992
Following dissemination from a primary tumor, viable cancer cells that lodge at secondary sites (2 sites) can persist for extended periods of time before going on to form clinically detectable disease. It is puzzling why tumor cells that have lost checkpoint control of the cell cycle and evaded death at the 1 tumor site should fail to grow at remote sites in both experimental models and patients. No one knows how such cells ultimately initiate growth and complete the process of metastatic colonization which can ultimately lead to death. Previously we identified a novel function for MKK4/JNKK1, as a metastasis-suppressor gene for prostate cancer. MKK4/JNKK1 is a dual-specificity kinase that activates the JNK and p38 MAP kinases in response to extracellular stimuli. We have recently shown that ectopic expression of MKK4/JNKK1 results in the context-dependent suppression of metastatic colonization, and that MKK4/JNKK1 protein is down-regulated in clinical disease. Our laboratory is now investigating three general lines of study: (1) Developing a detailed understanding of he signaling events and mechanisms involved in the survival and ultimate induction of growth of disseminated prostate, ovarian and breast cancer cells at metastatic sites; (2) Testing the effect of MKK4/JNKK1 s metastasis suppressor activity in the regulation of cell cycle progression and cell division in disseminated prostate, ovarian and breast cancer cells at metastatic sites; and (3) Exploring the potential contribution of societal interactions which may enable groups of cells to colonization metastatic sites more efficiently that single cells.