Critical Contribution of RAL GTPases to Growth and Survival of Breast Cancer Cells

Abstract

The monomeric Ral GTPases, RalA and RalB have been recognized as core components of the regulatory framework supporting tumorigenic transformation. Specifically, RalA is required to maintain anchorage independent proliferation while RalB is required to suppress apoptotic checkpoint activation. Here, we have defined the mechanistic contribution of RalB to cancer cell survival. We find that in normal human epithelia, a RalB/Sec5/TBK1 signal transduction cascade connects viral surveillance receptors to activation of host defense gene expression. We find that this pathway is aberrantly engaged by oncogene activation in tumors with the consequence of deflecting programmed cell death pathways that would normally engage in response to oncogene-induced stress. The obligate chronic activation of TBK1 kinase in breast cancer cells coupled with the absence of toxicity upon TBK1 inactivation in normal breast epithelia suggests this protein represents a facile therapeutic target.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2007
Accession Number
ADA478473

Entities

People

  • Tzuling Cheng

Organizations

  • University of Texas at Dallas

Tags

DTIC Thesaurus Topics

  • Anti-Infective Agents
  • Apoptosis
  • Biomedical And Dental Materials
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Central Nervous System
  • Chemistry
  • Epithelial Cells
  • Gene Expression
  • Infection
  • Mass Spectrometry
  • Neoplasms
  • Polymeric Films
  • Programmed Cell Death
  • Proteins

Readers

  • Molecular Biology and Genetics