Galectins: Matricellular glycan-binding proteins linking cell adhesion, migration, and survival

Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1123, Buenos Aires, Argentina.
Cellular and Molecular Life Sciences CMLS (Impact Factor: 5.81). 08/2007; 64(13):1679-700. DOI: 10.1007/s00018-007-7044-8
Source: PubMed


Galectins are a taxonomically widespread family of glycan-binding proteins, defined by at least one conserved carbohydrate-recognition domain with a canonical amino acid sequence and affinity for beta-galactosides. Because of their anti-adhesive as well as pro-adhesive extracellular functions, galectins appear to be a novel class of adhesion-modulating proteins collectively known as matricellular proteins (which include thrombospondin, SPARC, tenascin, hevin, and disintegrins). Accordingly, galectins can display de-adhesive effects when presented as soluble proteins to cells in a strong adhesive state. In this context, the de-adhesive properties of galectins should be considered as physiologically relevant as the proadhesive effects of these glycan-binding proteins. This article focuses on the roles of mammalian galectins in cell adhesion, spreading, and migration, and the crossregulation of these functions. Although careful attention should be paid when examining individual galectin functions due to overlapping distributions, these intriguing glycan-binding proteins offer promising possibilities for the treatment and intervention of a wide variety of pathological processes, including cancer, inflammation, and autoimmunity.

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Available from: María T Elola, Jul 25, 2015
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    • "The tandemrepeated types (galectin-4, -6, -8, -9, and -12) include galectins that have two non-identical CRDs linked by a short peptide. A number of functions have been proposed for galectins, including modulation of the immune system, activation of T-cell proliferation, induction of cell adhesion and inhibition of many types of tumors and cancers (Elola et al., 2007). In fish, relatively few types of lectins have been identified to date. "
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    ABSTRACT: Galectins belong to the family of galactoside-binding proteins and play a major role in the immune and inflammatory responses of vertebrates and invertebrates. The galectin family is divided into three sub-types based on molecular structure; prototypes, chimera types, and tandem-repeated types. We isolated and characterized the cDNA of galectin-8 (OnGal-8) in Nile tilapia (Oreochromis niloticus). OnGal-8 consisted of a 966 bp open reading frame (ORF) that encoded a 321 amino acid protein (43.47 kDa). Homology and phylogenetic tree analysis suggested the protein was clustered with galectin-8s from other animal species and shared at least 56.8% identity with salmon galectin-8. Structurally, the amino acid sequence included two distinct N-and C-terminus carbohydrate recognition domains (CRDs) of 135 and 133 amino acids, respectively, that were connected by a 39 amino acid polypeptide linker. The N-and C-CRDs contained two conserved WG-E-I and WG-E-T motifs, suggesting they have an important role in mediating the specific interactions between OnGal-8 and saccharide moieties such as-galactoside. The structure of OnGal-8 was characterized by a twofold symmetric pattern of 10-and 12-stranded antiparallel ß-sheets of both N-and C-CRDs, and the peptide linker presumably formed a random coil similar to the characteristic tandem-repeat type galectin. The expression of OnGal-8 in healthy fish was highest in the skin, intestine, and brain. Experimental challenge of Nile tilapia with S. agalactiae resulted in significant up-regulation of OnGal-8in the spleen after 5 d. Our results suggest that OnGal-8 is involved in the immune response to bacterial infection.
    Molecular Immunology 10/2015; DOI:10.1016/j.molimm.2015.09.012 · 2.97 Impact Factor
    • "These findings suggest that Gal1-induced EMT in HepG2 cells involves, at least in part, modulation of the MAPK signaling pathway. As mentioned above, by acting extracellularly, Gal1 can modulate cell adhesion, tumor growth, migration, angiogenesis, tumor-immune escape and metastasis (Elola et al., 2007; Ito et al., 2012). Nevertheless, Gal1 can also induce tumor cell transformation by acting intracellularly through binding to H- Ras to mediate Ras membrane anchorage (Paz et al., 2001). "
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    ABSTRACT: Galectin-1 (Gal1), a β-galactoside-binding protein abundantly expressed in tumor microenvironments, is associated with the development of metastasis in hepatocellular carcinomas (HCC). However, the precise roles of Gal1 in HCC cell invasiveness and dissemination are uncertain. Here, we investigated whether Gal1 mediate epithelial-mesenchymal transition (EMT) in HCC cells, a key process during cancer progression. We used the well-differentiated and low invasive HepG2 cells and performed 'gain-of-function' and 'loss-function' experiments by transfecting cells with Gal1 cDNA constructs or by siRNA strategies, respectively. Epithelial and mesenchymal markers expression, changes in apico-basal polarity, independent-anchorage growth and activation of specific signaling pathways were studied using Western blot, fluorescence microscopy, soft-agar assays and FOP/TOP flash reporter system. Gal1 up-regulation in HepG2 cells induced down-regulation of the adherens junction protein E-cadherin and increased expression of the transcription factor Snail, one of the main inducers of EMT in HCC. Enhanced Gal1 expression facilitated the transition from epithelial cell morphology towards a fibroblastoid phenotype and favored up-regulation of the mesenchymal marker vimentin in HCC cells. Cells overexpressing Gal1 showed enhanced anchorage-independent growth and loss of apico-basal polarity. Remarkably, Gal1 promoted Akt activation, β-catenin nuclear translocation, TCF4/LEF1 transcriptional activity and increased cyclin D1 and c-Myc expression, suggesting activation of the Wnt pathway. Furthermore, Gal1 overexpression induced E-cadherin downregulation through a PI3K/Akt-dependent mechanism. Our results provide the first evidence of a role of Gal1 as an inducer of EMT in HCC cells, with critical implications in HCC metastasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Cellular Physiology 06/2015; 230(6). DOI:10.1002/jcp.24865 · 3.84 Impact Factor
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    • "Galectins (Gals), a family of mammalian lectins, are involved in a wide spectrum of biological processes such as proliferation, apoptosis , adhesion, migration and cytokine secretion, among others (Elola et al. 2007; Liu and Rabinovich 2010). Moreover, Gals have immune regulatory functions and play important roles in the homeostasis of the immune system (Norling et al. 2009; Cattaneo et al. 2011). "
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    ABSTRACT: Galectins (Gals), a family of mammalian lectins, play diverse roles under physiological and pathological conditions. Here, we analyzed the tandem-repeat Gal-8 synthesis, secretion and effects on the endothelium physiology. Gal-8M and Gal-8L isoforms were secreted under basal conditions by human microvascular endothelial cells (HMEC-1). However, expression and secretion of the Gal-8M isoform, but not Gal-8L, were increased in response to bacterial lipopolysaccharide (LPS) stimulus and returned to control values after LPS removal. Similarly, cell surface Gal-8 exposure was increased after stimulation with LPS. To evaluate Gal-8 effects on the endothelium physiology, HMEC-1 cells were incubated in the presence of recombinant Gal-8M. Pretreated HMEC-1 cells became proadhesive to human normal platelets, indicating that Gal-8 actually activates endothelial cells. This effect was specific for lectin activity as it was prevented by the simultaneous addition of lactose, but not by sucrose. Endothelial cells also increased their exposition of von Willebrand factor after Gal-8 treatment, which constitutes another feature of cell activation that could be, in turn, responsible for the observed platelet adhesion. Several pro-inflammatory molecules were abundantly produced by Gal-8 stimulated endothelial cells: CXCL1 (GRO-α), GM-CSF, IL-6 and CCL5 (RANTES), and in a lower degree CCL2 (MCP-1), CXCL3 (GRO-γ) and CXCL8 (IL-8). In agreement, Gal-8M induced nuclear factor kappa B phosphorylation. Altogether, these results not only confirm the pro-inflammatory role we have already proposed for Gal-8 in other cellular systems but also suggest that this lectin is orchestrating the interaction between leukocytes, platelets and endothelial cells. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected] /* */
    Glycobiology 06/2014; 24(10). DOI:10.1093/glycob/cwu060 · 3.15 Impact Factor
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