The objective of this proposal is to apply systems biology techniques to the study of signal transduction in cancer progression. The first goal is to develop a novel approach to study signaling in complex systems by identifying global patterns in mRNA, protein expression and posttranslational modifications that report activation of signaling pathways. I will examine activation of the extracellular regulated kinase (ERK) pathway in melanoma progression because melanoma is a well-defined model of cancer progression that involves activation of Raf, MEK (MAPK/ERK kinase), and ERK at early stages. I will then apply this approach to determine whether Rho GTPases are important in melanoma progression, a question that is suggested by preliminary analysis of melanoma cell lines. The second goal of this proposal is to determine the functional significance of ERK and Rho family GTPase signaling in melanoma progression. Specific targets of ERK and Rho family pathways in melanoma progression will be examined to evaluate their contribution to cancer, in an effort to define the mechanisms by which signaling pathways direct cancer progression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA105796-02
Application #
6932356
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Lohrey, Nancy
Project Start
2004-07-16
Project End
2007-08-04
Budget Start
2005-07-16
Budget End
2006-08-04
Support Year
2
Fiscal Year
2005
Total Cost
$49,928
Indirect Cost
Name
University of Colorado at Boulder
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
Argast, G M; Croy, C H; Couts, K L et al. (2009) Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in melanoma cells. Oncogene 28:2697-709
Kabuyama, Yukihito; Litman, Elizabeth S; Templeton, Paul D et al. (2009) A mediator of Rho-dependent invasion moonlights as a methionine salvage enzyme. Mol Cell Proteomics 8:2308-20
Witze, Eric S; Litman, Elizabeth S; Argast, Gretchen M et al. (2008) Wnt5a control of cell polarity and directional movement by polarized redistribution of adhesion receptors. Science 320:365-9