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

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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.

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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

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Acknowledgments

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

Author information

Author notes

  1. T. S. Amsavardani

    Present address: Department of Oral Pathology, Indira Gandhi Institute of Dental Sciences, Pondicherry, India

Authors and Affiliations

  1. Central Research Laboratory, SDM College of Medical Sciences & Hospital, Manjushree Nagar, Sattur, Dharwad, 580 009, India

    Praveenkumar Shetty, Anil Bargale & Vidya S. Patil

  2. Department of Biochemistry, SDM College of Medical Sciences & Hospital, Manjushree Nagar, Sattur, Dharwad, 580 009, India

    Praveenkumar Shetty, Anil Bargale & Vidya S. Patil

  3. Karnataka Cancer Therapy and Research Institute, Hubli, India

    Basavraj R. Patil

  4. Department of Surgery, SDM College of Medical Sciences & Hospital, Dharwad, India

    Rajashekar Mohan

  5. Department of Pathology, SDM College of Medical Sciences & Hospital, Dharwad, India

    U. S. Dinesh

  6. Department of Molecular Medicine, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA

    Jamboor K. Vishwanatha

  7. Karnataka Institute of DNA Research, Dharwad, India

    Pramod B. Gai

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  1. Praveenkumar Shetty
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Correspondence to Praveenkumar Shetty.

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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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Shetty, P., Bargale, A., Patil, B.R. et al. Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth factor receptor signaling in Her-2 negative breast cancer cells. Mol Cell Biochem 411, 221–233 (2016). https://doi.org/10.1007/s11010-015-2584-y

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