Authors: Praveenkumar Shetty Anil Bargale Basavraj R Patil Rajashekar Mohan U S Dinesh Jamboor K Vishwanatha Pramod B Gai Vidya S Patil T S Amsavardani
Publish Date: 2015/10/05
Volume: 411, Issue: 1-2, Pages: 221-233
Abstract
Overexpression and activation of tyrosine kinase receptors like EGFR and Src regulate the progression and metastasis of Her2 negative breast cancer Recently we have reported the role of cell membrane interaction of phospholipidbinding protein annexin A2 AnxA2 and EGFR in regulating cellular signaling in the activation of angiogenesis matrix degradation invasion and cancer metastasis Betagalactosidespecific animal lectin galectin3 is an apoptosis inhibitor and cell surfaceassociated extracellular galectin3 also has a role in cell migration cancer progression and metastasis Similar expression pattern and membrane colocalization of these two proteins made us to hypothesize in the current study that galectin3 and AnxA2 interaction is critical for Her2 negative breast cancer progression By various experimental analyses we confirm that glycosylated AnxA2 at the membrane surface interacts with galectin3 Nlinked glycosylation inhibitor tunicamycin treatment convincingly blocked AnxA2 membrane translocation and its association with galectin3 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 galectin3 interaction at the cell surface This dissociation could downregulate Bcl2 family proteins cell proliferation and migration simultaneously triggering cell apoptosis Targeting this interaction of membrane surface glycoprotein and its animal lectin in Her2 negative breast cancer may be of therapeutic value
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