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Molecular and Cellular Biochemistry

, Volume 411, Issue 1–2, pp 221–233 | Cite as

Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth factor receptor signaling in Her-2 negative breast cancer cells

  • Praveenkumar Shetty
  • Anil Bargale
  • Basavraj R. Patil
  • Rajashekar Mohan
  • U. S. Dinesh
  • Jamboor K. Vishwanatha
  • Pramod B. Gai
  • Vidya S. Patil
  • T. S. Amsavardani
Article

Abstract

Overexpression and activation of tyrosine kinase receptors like EGFR and Src regulate the progression and metastasis of Her-2 negative breast cancer. Recently we have reported the role of cell membrane interaction of phospholipid-binding protein annexin A2 (AnxA2) and EGFR in regulating cellular signaling in the activation of angiogenesis, matrix degradation, invasion, and cancer metastasis. Beta-galactoside-specific animal lectin galectin-3 is an apoptosis inhibitor, and cell surface-associated extracellular galectin-3 also has a role in cell migration, cancer progression, and metastasis. Similar expression pattern and membrane co-localization of these two proteins made us to hypothesize in the current study that galectin-3 and AnxA2 interaction is critical for Her-2 negative breast cancer progression. By various experimental analyses, we confirm that glycosylated AnxA2 at the membrane surface interacts with galectin-3. N-linked glycosylation inhibitor tunicamycin treatment convincingly blocked AnxA2 membrane translocation and its association with galectin-3. To analyze whether this interaction has any functional relevance, we tried to dissociate this interaction with purified plant lectin from chickpea (Cicer arietinum agglutinin). This highly specific 30 kDa plant lectin could dissociate AnxA2 from endogenous lectin galectin-3 interaction at the cell surface. This dissociation could down-regulate Bcl-2 family proteins, cell proliferation, and migration simultaneously triggering cell apoptosis. Targeting this interaction of membrane surface glycoprotein and its animal lectin in Her-2 negative breast cancer may be of therapeutic value.

Keywords

AnxA2 Galectin-3 EGFR Animal lectin Her-2 Breast cancer 

Abbreviations

TNBC

Triple-negative breast cancer

EGFR

Epidermal growth factor receptor

Her-2

Epidermal growth factor receptor-2, ERbB-2

ER

Estrogen receptor

PR

Progesterone receptor

STAT

Signal transducer and activator of transcription

ERK

Extracellular signal-regulated kinases

RTK

Receptor tyrosine kinase

GAPDH

Glyceraldehyde-3 phosphate dehydrogenase

PAGE

Polyacrylamide gel electrophoresis

IHC

Immunohistochemistry

FBS

Fetal bovine serum

MTT

Methyl thiazol tetrazolium

FITC

Fluorescein isothiocyanate

tPA

Tissue-type plasminogen activator

BCA

Bicinchoninic acid

Notes

Acknowledgments

Authors like to acknowledge Mr. Harikrishna Ellanki for technical help.

Compliance with ethical standards

Conflicts of interests

The authors have declared that no competing interests exist.

Funding

This work was supported by Indian Council of Medical Research (ICMR) Ad hoc grant, IRIS No. 09390 to Dr. Praveenkumar Shetty, partly by SDM Institutional grant and seed funding from Karnataka Cancer Therapy and Research Institute, Hubli. The funders had no role in study design, data collection, and analysis, decision to publish or preparation of the manuscript.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Praveenkumar Shetty
    • 1
    • 2
  • Anil Bargale
    • 1
    • 2
  • Basavraj R. Patil
    • 3
  • Rajashekar Mohan
    • 4
  • U. S. Dinesh
    • 5
  • Jamboor K. Vishwanatha
    • 6
  • Pramod B. Gai
    • 7
  • Vidya S. Patil
    • 1
    • 2
  • T. S. Amsavardani
    • 8
  1. 1.Central Research LaboratorySDM College of Medical Sciences & HospitalDharwadIndia
  2. 2.Department of BiochemistrySDM College of Medical Sciences & HospitalDharwadIndia
  3. 3.Karnataka Cancer Therapy and Research InstituteHubliIndia
  4. 4.Department of SurgerySDM College of Medical Sciences & HospitalDharwadIndia
  5. 5.Department of PathologySDM College of Medical Sciences & HospitalDharwadIndia
  6. 6.Department of Molecular MedicineUniversity of North Texas Health Science Center at Fort WorthFort WorthUSA
  7. 7.Karnataka Institute of DNA ResearchDharwadIndia
  8. 8.Department of Oral PathologyIndira Gandhi Institute of Dental SciencesPondicherryIndia

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