Galectin-3 Regulates Expression Of E-Cadherin In Cancer Cells Mediated By Egfr

Galectins are a family of mammalian P-galactoside binding proteins, characterized by their affinity for p-galactosides and by a conserved sequence in the carbohydrate recognition domain (CRD) that binds to the carbohydrate portion of cell surface glycoproteins or glycolipids. Galectin-3 is the unique member of the chimera-type galectin subgroup and contains one CRD, which is connected to an extended non-lectin N-terminal domain. Galectin-3, a 31kDa glycoprotein, regulates cancer apoptosis, cell adhesion, cell proliferation and angiogenesis. Such a diverse influence of galectin-3 on cancer cell activities is due to its multiple sub-cellular localizations where it interacts with a range of different binding partners.During cancer metatasis, cell adhesion molecules (CAMs) are involved in multiple steps and regulate cell-cell and/or cell-ECM interactions. Based on the sequence homology and structure, CAM families includes cadherins, selectins, integrins, the immunoglobulin superfamily (Ig-SF), and lymphocyte homing receptors, such as CD44. E-cadherin, the prototype member of the classical cadherin family, is most important in maintaining epithelial polarity and integrity. Extracellularly, two E-cadherin molecules from adjacent cells are bound together by calcium ions on the five extracellular cadherin repeats to form a cishomodimer and comprise the adheren junctions. Intracellularly, E-cadherin is linked to the actin cytoskeleton through α-, β-, and p-120 catenin.Here, we will describe the relation between galectin-3 and E-cadherin. EGFR pathway are closely linked galectin-3 and E-cadherin, so we first discussed the EGF induced on the necessity of the contact. MTT assays showed that EGF stimulation or not, galectin 3 inhibitors,β-Lactose can inhibit proliferation of tumor cell A549, so EGF stimulation for galectin 3 antiapoptotic is irrelevant. However, Scratch experiments showed that EGF can induce the migration of A549 and Western blotting assays also showed that only exist in EGF, galectin 3 have an impact on the expression of E cadherin. Because E-cadherin mainly involved in tumor invasion and metastasis, we choose EGF stimulated by conducting follow-up experiments. Western blotting showed that in 15 min, the expression of p-EGFR was highest. To make the results more clearly, the follow-up experiment were induced using EGF 15 min.Western blotting showed under the EGF induction, in high expressed galectin 3 MCF-7 and HCT-116, β-Lactose reduced the expression of E-cadherin and β-catenin. In the lower expressed galectin-3 A549 cancer cells, β-Lactose had no effect on the expression of E-cadherin and β-catenin. These data demonstrated that the cell surface of galectin-3 promoted the expression of E-cadherin and β-catenin.Western blotting analysis indicated under the EGF induction, the exogenous recombinant galectin-3 reduced E-cadherin expression, but promoted β-catenin expression in A549. Meanwhile, in A549, nuclear and cytoplasmic extraction reagents assay proved that galectin-3 can promote the nuclear transport of P-catenin. Immune coprecipitation experiments showed that exogenous galectin-3 had no significant influence on complex E-cadherin/ β -catenin. These data demonstrated that Exogenous galectin-3 reduced the expression of E-cadherin, raised the β-catenin expression, promoted the β-catenin into the nucleus, but did not affect complexe E-cadherin/ β-catenin.To sum up, galectin-3 and E-cadherin have important inner link, and the distribution of the galectin 3 regulating E-cadherin are different.