Galectin-3 in angiogenesis and metastasis

Abstract

Galectin-3 is a member of the family of β-galactoside-binding lectins characterized by evolutionarily conserved sequences defined by structural similarities in their carbohydrate-recognition domains. Galectin-3 is a unique, chimeric protein consisting of three distinct structural motifs: (i) a short NH2 terminal domain containing a serine phosphorylation site; (ii) a repetitive proline-rich collagen-α-like sequence cleavable by matrix metalloproteases; and (iii) a globular COOH-terminal domain containing a carbohydrate-binding motif and an NWGR anti-death motif. It is ubiquitously expressed and has diverse biological functions depending on its subcellular localization. Galectin-3 is mainly found in the cytoplasm, also seen in the nucleus and can be secreted by non-classical, secretory pathways. In general, secreted galectin-3 mediates cell migration, cell adhesion and cell-cell interactions through the binding with high affinity to galactose-containing glycoproteins on the cell surface. Cytoplasmic galectin-3 exhibits anti-apoptotic activity and regulates several signal transduction pathways, whereas nuclear galectin-3 has been associated with pre-mRNA splicing and gene expression. Its unique chimeric structure enables it to interact with a plethora of ligands and modulate diverse functions such as cell growth, adhesion, migration, invasion, angiogenesis, immune function, apoptosis and endocytosis emphasizing its significance in the process of tumor progression. In this review, we have focused on the role of galectin-3 in tumor metastasis with special emphasis on angiogenesis.

Demethylation drug 5-Aza-2′-deoxycytidine-induced upregulation of miR-200c inhibits the migration, invasion and epithelial-mesenchymal transition of clear cell renal cell carcinoma in vitro

“…MicroRNAs (miRs) are a type of small non-coding RNA (19)(20)(21)(22)(23)(24)(25) nucleotides) that possess prominent roles in the regulation of genes (6). MiRs typically inhibit gene expression by directly binding the 3'-untranslated region of their target messenger (m)RNAs, causing repression of translation or mRNA degradation (7).…”

Endo-F3 Glycosynthase Mutants Enable Chemoenzymatic Synthesis of Core-fucosylated Triantennary Complex Type Glycopeptides and Glycoproteins

“…Galectin-3 recognizes ␤-galactoside-terminating glycoconjugates in biological systems and plays important roles in a number of biological processes, including cell adhesion, autoimmunity, and cancer metastasis (78). The fact that the new triantennary complex type glycoform demonstrates much higher affinity for galectin-3 than that of the commercial rituximab suggests that the glycosylation-remodeled antibody may confer novel properties to the antibodies in vivo.…”

Circulating galectin-3 correlates with angiogenetic factors, indicators of nutritional condition and systemic inflammation in patients with thyroid cancer

“…Thus, forming metastatic foci involves complicated phenomenon, regulated by multiple interactions between tumor cells and host cells 31) . Galectin-3 has been reported to play a role in each of the following steps: anti-apoptosis, tumor proliferation, tumor progression, cellular adhesion, and angiogenesis [11][12][13][14][15] . Consistent with Chen et al's findings in an in vitro examinations 18) , we observed correlations in this study between galectin-3 and angiogenetic factors, such as IL-6, G-CFS, and sICAM-I.…”

“…Galectin-3, a beta-galactoside binding lectin, is a moonlighting protein, implicated in cell growth, differentiation, apoptosis, adhesion, malignant transformation, RNA processing, and angiogenesis [11][12][13][14][15] . Accumulating evidences have revealed an elevated concentration of serum galectin-3 in various cancers including breast 16) , colorectal 17,18) , stomach 19) , lung 16) , bladder 20) , head and neck 21) , liver 22) , melanoma 23) , pancreatic 24) , and thyroid [25][26][27][28][29] .…”