Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

Abstract

It has been suggested that PHSCN inhibits metastatic invasion by forming a covalent, disulfide bond with a cysteine residue on the beta1 (alpha-5-beta-1) subunit of alpha5 beta1 (alpha-5 beta-1) integrin1. However, these studies were performed with purified alpha-5-beta-1 integrin, which also produces evidence of covalent bond formation with the alpha-5 subunit (tandem mass spectroscopy data not shown). Hence, the specificity of the reported interaction between PHSCN and the beta-1 subunit1 is suspect. Moreover, the cysteine rich beta-1 subunit can heterodimerize with 12 distinct alpha integrin subunits2, forming integrins that function in many pathways. In contrast, the alpha-5 subunit interacts uniquely with the beta-1 subunit2 to induce invasion and support adhesion 3-5; thus it is a much more desirable target.

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Document Details

Document Type
Technical Report
Publication Date
Nov 01, 2015
Accession Number
ADA626547

Entities

People

  • Donna L. Livant

Organizations

  • University of Michigan

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biological Factors
  • Blood
  • Bone Diseases
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Chemical Synthesis
  • Chemistry
  • Confocal Microscopy
  • Diseases And Disorders
  • Endothelial Cells
  • Mass Spectrometry
  • Neoplasms
  • Peptides
  • Proteins

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and Cellular Biochemistry