title: Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth factor receptor signaling in Her-2 negative breast cancer cells.
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.
authors.affiliation: Central Research Laboratory, SDM College of Medical Sciences & Hospital, Manjushree Nagar, Sattur, Dharwad, 580 009, India. shettybp@hotmail.com.|Department of Biochemistry, SDM College of Medical Sciences & Hospital, Manjushree Nagar, Sattur, Dharwad, 580 009, India. shettybp@hotmail.com.
authors.forename: Praveenkumar
authors.identifier: http://orcid.org/0000-0002-1201-2637
authors.initials: P
authors.lastname: Shetty
authors.affiliation: Central Research Laboratory, SDM College of Medical Sciences & Hospital, Manjushree Nagar, Sattur, Dharwad, 580 009, India.|Department of Biochemistry, SDM College of Medical Sciences & Hospital, Manjushree Nagar, Sattur, Dharwad, 580 009, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Bargale
authors.affiliation: Karnataka Cancer Therapy and Research Institute, Hubli, India.
authors.forename: Basavraj R
authors.initials: BR
authors.lastname: Patil
authors.affiliation: Department of Surgery, SDM College of Medical Sciences & Hospital, Dharwad, India.
authors.forename: Rajashekar
authors.initials: R
authors.lastname: Mohan
authors.affiliation: Department of Pathology, SDM College of Medical Sciences & Hospital, Dharwad, India.
authors.forename: U S
authors.initials: US
authors.lastname: Dinesh
authors.affiliation: Department of Molecular Medicine, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
authors.forename: Jamboor K
authors.initials: JK
authors.lastname: Vishwanatha
authors.affiliation: Karnataka Institute of DNA Research, Dharwad, India.
authors.forename: Pramod B
authors.initials: PB
authors.lastname: Gai
authors.affiliation: Central Research Laboratory, SDM College of Medical Sciences & Hospital, Manjushree Nagar, Sattur, Dharwad, 580 009, India.|Department of Biochemistry, SDM College of Medical Sciences & Hospital, Manjushree Nagar, Sattur, Dharwad, 580 009, India.
authors.forename: Vidya S
authors.initials: VS
authors.lastname: Patil
authors.affiliation: Department of Oral Pathology, Indira Gandhi Institute of Dental Sciences, Pondicherry, India.
authors.forename: T S
authors.initials: TS
authors.lastname: Amsavardani
mesh_terms: D017306:Annexin A2 / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D037502:Galectin 3 / Q000378:metabolism*; D018734:Genes, erbB-2; D006031:Glycosylation; D006801:Humans; D015398:Signal Transduction; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D017306:Annexin A2; D037502:Galectin 3; D014415:Tunicamycin; D004815:Epidermal Growth Factor
keywords: Animal lectin; AnxA2; Breast cancer; EGFR; Galectin-3; Her-2