Galectin-1: A bifunctional regulator of cellular proliferation (original) (raw)
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Galectin-1: A bifunctional regulator of cell proliferation
Galectin-1 has demonstrated a diverse range of activities in relation to cell survival and proliferation. In different circumstances, it acts as a mitogen, as an inhibitor of cell proliferation, and as a promoter of cellular apoptosis. Many of these activities, particularly the mitogenic and apoptotic responses, follow from the interaction of galectin-1 with cellsurface β-galactoside ligands, but there is increasing evidence for protein-protein interactions involving galectin-1, and for a β-galactoside-independent cytostatic mechanism. The bifunctional nature of galectin-1, in conjunction with other experimental variables, makes it difficult to assess the overall outcomes and significance of the growth-regulatory actions in many previous investigations. There is thus a need for well-defined experimental cross-correlation of observations, for which specific loss-of-function galectin-1 mutants will be invaluable. Unsurprisingly, in view of this background, the interpretation of the actions of galectin-1 in developmental situations, both normal and neoplastic, is often very complex. Published in 2004. Keywords: galectin-1, cell regulation, growth inhibition, differentiation, cancer, metastasis
Galectins in cell growth and apoptosis
Cellular and Molecular Life Sciences (CMLS), 2003
Fourteen members of the galectin family, proteins with conserved carbohydrate-recognition domains that bind b-galactoside, have been cloned and more are expected to be discovered in the near future. Many aspects of galectin biology have been thoroughly explored, and functional studies have implicated these proteins in cell growth, differentiation and apoptosis, in addition to CMLS Cellular and Molecular Life Sciences cell adhesion, chemoattraction and cell migration. In some cases a galectin can either promote or suppress cell growth, depending on the cell types and doses used. Galectin-3 is the only member known so far to inhibit apoptosis, while galectin-1, -7 and -9 promote this cellular process. Galectins can act either extracellularly or intracellularly to exert effects on cell growth and apoptosis.
Biphasic modulation of cell growth by recombinant human galectin-1
Biochimica Et Biophysica Acta-molecular Cell Research, 1996
Human soluble galactose-binding lectin (galectin-1) has been expressed as an Escherichia coli fusion protein, following the amplification by polymerase chain reaction of cDNA prepared from a human osteosarcoma cell line. The fusion protein is a functional /3-galactoside-binding lectin, as is the recombinant galectin when purified from the cleaved fusion protein. The recombinant galectin has a biphasic effect on cell proliferation. Unlike the fusion protein, it functions as a human cell growth inhibitor, confirming earlier findings with natural human galectin-1, though it is less effective than the natural galectin. This reaction is not significantly inhibited by lactose, and is thus largely independent of the /3-galactoside-binding site. At lower concentrations, recombinant galectin-I is mitogenic, this activity being susceptible to inhibition by lactose, and thus attributable to the /3-galactoside-binding ability of the protein. Some tumour cells are susceptible to the growth-inhibitory effect, and the galectin-1 gene is expressed in both normal and tumour cells.
Galectin-3: a potential target for cancer prevention
Trends in carbohydrate research, 2011
Protein-carbohydrate interactions play significant role in modulating cell-cell and cell-extracellular matrix interactions, which, in turn, mediate various biological processes such as growth regulation, immune function, cancer metastasis, and apoptosis. Galectin-3, a member of the β-galactoside-binding protein family, is found multifunctional and is involved in normal growth development as well as cancer progression and metastasis, but the detailed mechanisms of its functions are not well understood. This review discusses its structure, binding properties, transcriptional regulation and roles in homotypic/heterotypic cell adhesion, angiogenesis and apoptosis.
Galectins: structure, function and therapeutic potential
Expert Reviews in Molecular Medicine, 2008
Galectins are a family of animal lectins that bind β-galactosides. Outside the cell, galectins bind to cell-surface and extracellular matrix glycans and thereby affect a variety of cellular processes. However, galectins are also detectable in the cytosol and nucleus, and may influence cellular functions such as intracellular signalling pathways through protein–protein interactions with other cytoplasmic and nuclear proteins. Current research indicates that galectins play important roles in diverse physiological and pathological processes, including immune and inflammatory responses, tumour development and progression, neural degeneration, atherosclerosis, diabetes, and wound repair. Some of these have been discovered or confirmed by using genetically engineered mice deficient in a particular galectin. Thus, galectins may be a therapeutic target or employed as therapeutic agents for inflammatory diseases, cancers and several other diseases.
Human recombinant galectin-1 as a potential growth modulator
Subscription resource available via Digital Dissertations only. Human galectin-1 is a soluble form of lectin known to play a role in various cellular processes by mediating recognition events in which glycoconjugates are implicated. As a number of studies have shown that galectin-1 is a growth inhibitor (Wells and Mallucci, 1991; Manilal et al., 1993), the starting hypothesis for this thesis was that galectin-1 might be a substrate for a growth-related proteinase (GRP). The intention was to identify the mechanism of action responsible for this growth-inhibitory property by looking at the effect of galectin treatment on the expression of the c-fos proto-oncogene. The structure of the recombinant galectin-1 molecule was investigated in mass spectrometry determinations. Galectin-1 was further characterised in hemagglutination, cellular growth, cytotoxicity, proteolysis and cellular degradation experiments. Even though the recombinant galectin-1 was not identical with the natural protei...
Galectin-1: biphasic growth regulation of Leydig tumor cells
Glycobiology, 2006
Galectin-1 (Gal-1) is a widely expressed b-galactosidebinding protein that exerts pleiotropic biological functions. To gain insight into the potential role of Gal-1 as a novel modulator of Leydig cells, we investigated its effect on the growth and death of MA-10 tumor Leydig cells. In this study, we identified cytoplasmic Gal-1 expression in these tumor cells by cytofluorometry. DNA fragmentation, caspase-3,-8, and-9 activation, loss of mitochondrial membrane potential (DYm), cytochrome c (Cyt c) release, and FasL expression suggested that relatively high concentrations of exogenously added recombinant Gal-1 (rGal-1) induced apoptosis by the mitochondrial and death receptor pathways. These pathways were independently activated, as the presence of the inhibitor of caspase-8 or-9 only partially prevented Gal-1-effect. On the contrary, low concentrations of Gal-1 significantly promoted cell proliferation, without inducing cell death. Importantly, the presence of the disaccharide lactose prevented Gal-1 effects, suggesting the involvement of the carbohydrate recognition domain (CRD). This study provides strong evidence that Gal-1 is a novel biphasic regulator of Leydig tumor cell number, suggesting a novel role for Gal-1 in the reproductive physiopathology.
Glycobiology, 2008
The galectin family of β-galactoside binding lectins is involved in normal and pathological processes. Altered expression of galectin-3 has been described in many cancers, and studies of cancer cell lines have implicated this lectin in various aspects of the tumorigenic cascade. The goal of this report was to directly assess the importance of galectin-3 in tumor biology by introducing the galectin-3 null mutation (galectin-3 −/−) into mouse lines genetically programmed to develop cancers. We used two mouse models of human intestinal cancer, the Apc Min and Apc 1638N lines, to study tumor initiation and tumor progression. We also crossed the galectin-3 −/− mice with PyMT transgenic animals, a model in which primary mammary gland tumors give rise to lung metastases at high frequency. Unexpectedly, we show that the absence of galectin-3 does not affect the evolution of the disease in any of these three situations.
Expression of galectin-3 modulates T-cell growth and apoptosis
Proceedings of the National Academy of Sciences, 1996
Galectin-3 is a member of a large family of ,B-galactoside-binding animal lectins. It has been shown that the expression of galectin-3 is upregulated in proliferating cells, suggesting a possible role for this lectin in regulation of cell growth. Previously, we have shown that T cells infected with human T-cell leukemia virus type I express high levels of galectin-3, in contrast to uninfected cells, which do not express detectable amounts of this protein. In this study, we examined growth properties of human leukemia T cells transfected with galectin-3 cDNA, and thus constitutively overexpressing this lectin. Transfectants expressing galectin-3 displayed higher growth rates than control transfectants, which do not express this lectin. Furthermore, galectin-3 expression in these cells confers resistance to apoptosis induced by anti-Fas antibody and staurosporine. Galectin-3 was found to have significant sequence similarity with Bcl-2, a well-characterized suppressor of apoptosis. In particular, the lectin contains the NWGR motif that is highly conserved among members of the Bcl-2 family and shown to be critical for the apoptosis-suppressing activity. We further demonstrated that galectin-3 interacts with Bcl-2 in a lactose-inhibitable manner. We conclude that galectin-3 is a regulator of cell growth and apoptosis and it may function through a cell death inhibition pathway that involves Bcl-2.