The Role of CXCR4 and Arrestins in Breast Cancer Signaling and Apoptosis

Abstract

We use the N-formyl peptide receptor (FPR) as a model for G protein-coupled receptor (GPCR) activity in the absence of arrestins. GPCRs are beginning to take center stage in understanding cancer metastasis specifically breast cancer metastasis. Also GPCRs are integral to cell migration another important feature of metastasis. Arrestin is a major player in GPCR trafficking and signaling both at the cell surface and post-endocytically. Therefore understanding GPCR function in the absence of arrestins may lead to novel chemotherapeutics for the treatment of breast cancer. We use the FPR as a model for the system we proposed in our original submission as it is a member of the same receptor family reagents are available that make the research methods easier and the same fundamental questions can be answered about G protein-coupled receptors (GPCR) and arrestins in breast cancer. We have previously found mutants of arrestin the do not rescue FPR-mediated apoptosis. Also these mutants show trafficking defects and may be related to AP-2 a regulator of cellular trafficking. In this report we outline further experiments performed to elucidate to role of AP-2 in FPR/arrestin function to better understand the mechanism of FPR-mediated apoptosis. In addition we have found other mutants of arrestin (some of which have deficient interaction with Src kinase) that also do not rescue FPR-mediated apoptosis. We show data that helps us understand the role of Src kinase in this process as well. Finally data from all three tasks lead to the hypothesis that there may be multiple independent steps gone awry in FPR-mediated apoptosis in the absence of arrestins. These steps seem likely to be regulated by interaction and signaling form arrestins Src kinase AND AP-2 perhaps in combination.

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2006
Accession Number
ADA448129

Entities

People

  • Brant M Wagener

Organizations

  • University of New Mexico

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Apoptosis
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cells
  • Diseases And Disorders
  • Fluorescence
  • Inhibitors
  • Integrals
  • Kinases
  • Metastasis
  • Microscopy
  • Migration
  • Molecules
  • Neoplasms
  • New Mexico

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Cellular and Molecular Pathways of Apoptosis.
  • Oncology