Accumulating evidence from both cell and animal-based model systems indicates the Ras-like small GTP-binding proteins RalA and RalB are core components of a regulatory framework supporting tumorigenic transformation. Recently we have established discrete but interlocking contributions of these highly related G-proteins to the regulation of both cancer and cell proliferation and survival. Specifically, chronic activation of RalA is required to maintain anchorage-independent proliferation, while RalB is required to deflect cell-death checkpoint activation. This proposal is directed at defining the composition, organization, and function of cell regulatory networks engaged by Ral family G-proteins. Our focus is on the dominant RalA and RalB effector pathways that directly participate in oncogenic transformation.
Our specific aims are 1) identification of the effector pathway(s) mediating RalA support of anchorage-independent proliferation, 2) defining the mechanistic contribution of RalB signaling to cancer cell survival, and 3) evaluating the consequences of perturbations in RalA/RalB signaling networks to tumor initiation and/or progression in xenograft and organotypic model systems.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA129451-04S1
Application #
8117839
Study Section
Tumor Cell Biology Study Section (TCB)
Program Officer
Ogunbiyi, Peter
Project Start
2007-09-07
Project End
2012-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
4
Fiscal Year
2010
Total Cost
$64,948
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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