Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth factor receptor signaling in Her-2 negative breast cancer cells
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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DOI：
10.1007/s11010-015-2584-y
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发表时间：
2015
影响因子：
4.3
通讯作者：
P. Shetty;Anil Bargale;B. R. Patil;Rajashekar Mohan;US Dinesh;J. Vishwanatha;P. Gai;V. Patil;T. S. Amsavardani
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文献类型：
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作者：
P. Shetty;Anil Bargale;B. R. Patil;Rajashekar Mohan;US Dinesh;J. Vishwanatha;P. Gai;V. Patil;T. S. Amsavardani
酪氨酸激酶受体EGFR和Src的过度表达和激活调控HER-2阴性乳腺癌的进展和转移。最近，我们报道了磷脂结合蛋白Annexin A2(AnxA2)和EGFR的细胞膜相互作用在激活血管生成、基质降解、侵袭和肿瘤转移中调节细胞信号的作用。β-半乳糖苷特异的动物凝集素Galectin-3是一种凋亡抑制因子，细胞表面相关的细胞外Galectin-3也在细胞迁移、肿瘤进展和转移中发挥作用。这两种蛋白的相似表达模式和膜共定位使我们在目前的研究中假设Galectin-3和AnxA2的相互作用在HER-2阴性乳腺癌的进展中起关键作用。通过各种实验分析，我们证实了膜表面糖基化的AnxA2与Galectin-3相互作用。N-连接糖基化抑制剂衣霉素治疗令人信服地阻断AnxA2膜转位及其与Galectin-3的关系。为了分析这种相互作用是否具有任何功能相关性，我们试图将这种相互作用与从鹰嘴豆中纯化的植物凝集素(西瓜凝集素)分离。这种高度特异的30 kDa植物凝集素可以将AnxA2从细胞表面内源凝集素Galectin-3的相互作用中解离出来。这种解离可以下调Bcl2家族蛋白、细胞增殖和迁移，同时引发细胞凋亡。在HER-2阴性乳腺癌中，靶向这种膜表面糖蛋白及其动物凝集素的相互作用可能具有治疗价值。
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.