Galectin-4

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External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
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Wikidata
View/Edit Human

Galectin-4 is a protein that in humans is encoded by the LGALS4 gene.

The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. LGALS4 is an S-type lectin that is strongly underexpressed in colorectal cancer. The 323-amino acid LGALS4 protein contains 2 homologous, approximately 150-amino acid carbohydrate recognition domains and all amino acids typically conserved in galectins.

Structure

Gal 4 belongs to the family of galectin. Among various structure of galectins like dimeric, tandem or chimera, Gal-4 is tandem in its structure, so they contains at least two distinct carbohydrate recognising domains (CRD) within one polypeptide, thus are said to be intrinsically divalent. The CRDs are linked with a small peptide domain.

Protein name

Recommended name:Galectin-4, Short name: Gal-4 Alternative name(s):

Antigen NY-CO-27
L-36 lactose-binding protein, Short name: L36L
Lactose-binding lectin 4

Location (In human Body)

Gal-4 is generally found in stomach and intestine.

Functions

Gal-4 has binding ability with high affinity to lipid rafts suggesting a role in protein delivery to cells

Plus they can perform lots of Physiological functional as follows:

Gal-4 enhances the stabilization of lipid raft

Gal-4 participates in apical trafficking

Gal-4 has bactericidal activity against bacteria expressing blood group antigen

Gal-4 promotes intestinal wound healing

Gal-4 promotes growth of axon and myelination in neuron

Clinical Significance

Gal-4 and cancer

Gal-4 which has been detected in many cancer has involved in association with the development and sequence of pancreatic carcinoma, hepatocellular carcinoma, Colorectal cancer (CRC), breast carcinoma, gastric cancer, and lung cancer (Rechreche et al., 1997; Hippo et al., 2001; Hayashi et al., 2013; Belo et al., 2013; Cai et al., 2014). Afterall, it plays contradictory roles in different type of cancer cell. In addition to that, it has been found in serum of some cancer patients (Kim et al., 2013; Cai et al., 2014; Barrow et al., 2011; Barrow et al., 2013). Till now, in spite of a number of published data regarding galectin-4 expression in cancer, the available information has remained very much limited. Among these cancers, only the role of galectin-4 in CRC development has been revealed explicitly.

The utility of CEA (Carcinoembryonic antigen) and CA19-9 as colorectal carcinoma (CRC) markers is limited and development of additional reliable markers is under investigation. Circulating levels of galectin-1/-3/-4 in CRC patients were importantly higher compared to those in controls. Gal-1 and gal-4 levels significantly decreased after having surgery (P<0.01), and the level of gal-4 in most patients fell below the cut-off value. The levels of circulating gal-4 significantly increased as the tumor stage progressed (P<0.001), whereas those for galectin-1 were relatively high from an early stage. Combined use of gal-4 with CEA and/or CA19-9 distinctly increased the proportion of CRC patients who were positive for tumor markers (from 33.3 to 59.0% for CEA and from 17.1 to 51.4% for CA19-9). Our data show that galectin-4 may be a tumor marker for use in patient follow-up, while galectin-1 could be used for tumor screening. In particular, galectin-4 can be useful as a complementary marker when combined with CEA/CA19-9 to improve CRC follow-up

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Gal-4 and intestinal inflammation

Gal-4 was demonstrated to worsen the condition of intestinal inflammation by directly inducing the CD4+ T cells (cluster of differentiation 4) to produce IL-6(Interleukin) on TCR(T-cell receptor) mutational colitis model (Hokama et al., 2004). IL-6, a well-known inflammatory cytokine, could exacerbate intestinal inflammation in the presence of impaired mucosal barrier or injury to the mucosa. Furthermore, IL-6 was also confirmed to enhance the expression of B-cell lymphoma-2(Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) through activating the STAT3(Signal transducer and activator of transcription) signal pathway, thus inhibiting the apoptosis of CD4+ T cells, and leading to sustainable development of IBD (Atreya et al., 2000; Allocca et al., 2013; Waldner and Neurath, 2014). Gal-4 may directly interact with the CD4+ T cells through binding to the immunological synapse, which is a specific activator of the protein kinase C(PKC) θ-associated signaling cascade in lipid raft (Hokama et al., 2004; Nagahama et al., 2008). Through activating the PKC -associated pathway, galectin-4 stimulates the production of IL-6, therefore exacerbates intestinal inflammation. Anyway, it is not sure which receptor on intestinal CD4+ T cells particularly crosslinks with gal-4. It was found that an inducible colitis-associated glycome (CAG), which contains an immature (nonsialylated) core-1 O-glycan expressed by CD4+ T cells, was identified as a ligand of gal-4 under intestinal inflammatory conditions (Nishida et al., 2012). Thus, gal-4 may activate the PKCθ by binding to CAG and, then contributing to aggravation of colitis. In consistent with this, gal-4, which shows a high affinity to immature O-glycan (Ideo et al., 2002; Blixt et al., 2004), has been shown to exacerbate an experimental chronic colitis (Hokama et al., 2004). Nevertheless, Paclik D et al. demonstrated that gal-4 could induce T cell apoptosis by binding to the CD3 epitope at T cells surface on wild-type colitis model. Once binding to this epitope, gal-4 promotes apoptosis of T cells in calpain-dependent manner and reduces the secretion of cytokines including IL-6, IL-8, IL-10, and IL-17, and then improving the inflammation (Paclik et al., 2008a). Another research found that the role of gal-4 varied in different experimental colitis models (Mathieu et al., 2008). Based on the existing data, we can conclude that gal-4 may exacerbate intestinal inflammation in TCR mutational colitis model, while ameliorate intestinal inflammation in wild-type colitis model

Further reading

• Huflejt ME, Jordan ET, Gitt MA, et al. (1997). "Strikingly different localization of galectin-3 and galectin-4 in human colon adenocarcinoma T84 cells. Galectin-4 is localized at sites of cell adhesion". J. Biol. Chem. 272 (22): 14294–303. doi:10.1074/jbc.272.22.14294. PMID 9162064.
• Rechreche H, Mallo GV, Montalto G, et al. (1997). "Cloning and expression of the mRNA of human galectin-4, an S-type lectin down-regulated in colorectal cancer". Eur. J. Biochem. 248 (1): 225–30. doi:10.1111/j.1432-1033.1997.00225.x. PMID 9310382.
• Ideo H, Seko A, Ohkura T, et al. (2002). "High-affinity binding of recombinant human galectin-4 to SO(3)(−)-->3Galbeta1-->3GalNAc pyranoside". Glycobiology. 12 (3): 199–208. doi:10.1093/glycob/12.3.199. PMID 11971864.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Ideo H, Seko A, Yamashita K (2005). "Galectin-4 binds to sulfated glycosphingolipids and carcinoembryonic antigen in patches on the cell surface of human colon adenocarcinoma cells". J. Biol. Chem. 280 (6): 4730–7. doi:10.1074/jbc.M410362200. PMID 15546874.
• Delacour D, Gouyer V, Zanetta JP, et al. (2005). "Galectin-4 and sulfatides in apical membrane trafficking in enterocyte-like cells". J. Cell Biol. 169 (3): 491–501. doi:10.1083/jcb.200407073. PMC 2171948. PMID 15883199.
• Stowell SR, Karmakar S, Stowell CJ, et al. (2007). "Human galectin-1, -2, and -4 induce surface exposure of phosphatidylserine in activated human neutrophils but not in activated T cells". Blood. 109 (1): 219–27. doi:10.1182/blood-2006-03-007153. PMC 1785076. PMID 16940423.
• Ideo H, Seko A, Yamashita K (2007). "Recognition mechanism of galectin-4 for cholesterol 3-sulfate". J. Biol. Chem. 282 (29): 21081–9. doi:10.1074/jbc.M703770200. PMID 17545668.