87P - Inhibition of triple negative and herceptin-resistant breast cancer proliferation and migration by annexin A2 antibodies

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Basic Science
Breast Cancer
Presenter Jamboor Vishwanatha
Citation Annals of Oncology (2015) 26 (suppl_3): 29-30. 10.1093/annonc/mdv120
Authors J.K. Vishwanatha, P. Chaudhary
  • Molecular And Medical Genetics And Institute For Cancer Research, University of North Texas Health Science Center, 76107 - Fort Worth/US



Background: Annexin A2 (AnxA2), a calcium-dependent phospholipid binding protein, is abundantly present at the surface of triple-negative and Herceptin-resistant breast cancer cells. Interactions between cell-surface AnxA2 and tyrosine kinase receptors have an important role in the tumour microenvironment and act together to enhance tumour growth. The mechanism supporting this role is still unknown.

Methods: The membrane function of AnxA2 was blocked by incubating cells with anti-AnxA2 antibodies. Western blotting, immunoprecipitation, immunofluorescence, 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), flow cytometry, clonogenic, and wound-healing assays were performed in this study.

Results: We demonstrate that in triple-negative and Herceptin-resistant breast cancer cells a large amount of AnxA2 is specifically translocated to the outer membrane domain. In addition, AnxA2 interacts with extracellular domain of epidermal growth factor receptor (EGFR) at the cell surface and has an important role in cancer cell proliferation and migration by modulating EGFR functions. Blocking AnxA2 function at the cell surface by anti-AnxA2 antibody suppressed the EGF-induced EGFR tyrosine phosphorylation and internalization by blocking its homodimerization. Furthermore, addition of AnxA2 antibody significantly inhibited the EGFR-dependent PI3K-AKT and Raf-MEK-ERK downstream pathways under both EGF-induced and basal growth conditions, resulting in lower cell proliferation and migration.

Conclusions: These findings suggest that cell-surface AnxA2 has an important regulatory role in EGFR-mediated oncogenic processes by keeping EGFR signaling events in an activated state. Therefore, AnxA2 could potentially be used as a therapeutic target in triple-negative and Herceptin-resistant breast cancers.

Acknowledgment: Research reported in this publication was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number P20MD006882

Disclosure: All authors have declared no conflicts of interest.