Interrogating Spatio-Mechanical EphA2 Signaling in Cancer

Abstract

EphA2 is a receptor tyrosine kinase (RTK) overexpressed in many breast cancers. We have found that upon binding to its native ligand, ephrinA1, EphA2 is reorganized into large-scale clusters. Disrupting this clustering alters downstream signaling events, suggesting that this is a mechanosensitive pathway. Now, our goal is to elucidate how the mechanical properties of a cell and its environment play a role in the EphA2 regulatory system and how this mechanical sensing affects the malignancy of cancer cells. We have found that EphA2 clustering modulates both endocytosis and a PI3K signaling pathway. We have also developed a novel platform for screening small molecule inhibitors that may target other cellular processes, but affect EphA2 phenotypes which, we believe, are important in malignancy. Together, these results provide promising insight into linking the EphA2 mechanosensitive pathway to breast cancer malignancy.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2012
Accession Number
ADA567274

Entities

People

  • Jay Groves

Organizations

  • University of California, Berkeley

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Cancer
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Cytoskeleton
  • Department Of Defense
  • Immune System
  • Intercellular Junctions
  • Lymphocytes
  • Materials Science
  • Medical Personnel
  • Membrane Lipids
  • Metallic Nanoparticles
  • Proteins
  • Stem Cells

Fields of Study

  • Biology

Readers

  • Molecular and Cellular Biochemistry
  • Oncology (Cancer Research).