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

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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.

Original languageEnglish
Pages (from-to)221-233
Number of pages13
JournalMolecular and Cellular Biochemistry
Volume411
Issue number1-2
DOIs
StatePublished - 1 Jan 2016

Fingerprint

Galectin 3
Annexins
Epidermal Growth Factor Receptor
Annexin A2
Cell Communication
Cells
Breast Neoplasms
Lectins
Plant Lectins
Membranes
Cicer
Membrane Glycoproteins
Neoplasm Metastasis
Cell Movement
Chemical activation
Apoptosis
Cell signaling
Glycosylation
Tunicamycin
Agglutinins

Keywords

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

Cite this

Shetty, Praveenkumar ; Bargale, Anil ; Patil, Basavraj R. ; Mohan, Rajashekar ; Dinesh, U. S. ; Vishwanatha, Jamboor K. ; Gai, Pramod B. ; Patil, Vidya S. ; Amsavardani, T. S. / Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth factor receptor signaling in Her-2 negative breast cancer cells. In: Molecular and Cellular Biochemistry. 2016 ; Vol. 411, No. 1-2. pp. 221-233.
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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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Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth factor receptor signaling in Her-2 negative breast cancer cells. / Shetty, Praveenkumar; Bargale, Anil; Patil, Basavraj R.; Mohan, Rajashekar; Dinesh, U. S.; Vishwanatha, Jamboor K.; Gai, Pramod B.; Patil, Vidya S.; Amsavardani, T. S.

In: Molecular and Cellular Biochemistry, Vol. 411, No. 1-2, 01.01.2016, p. 221-233.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Shetty, Praveenkumar

AU - Bargale, Anil

AU - Patil, Basavraj R.

AU - Mohan, Rajashekar

AU - Dinesh, U. S.

AU - Vishwanatha, Jamboor K.

AU - Gai, Pramod B.

AU - Patil, Vidya S.

AU - Amsavardani, T. S.

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AB - 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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