| 2005 |
Galectin-4 is a major component of detergent-resistant membranes (lipid rafts) in polarized HT-29 5M12 enterocyte-like cells and is found in post-Golgi carrier vesicles. RNAi-mediated depletion of galectin-4 causes intracellular accumulation of apical (but not basolateral) membrane markers and alters DRM association of apical proteins. Sulfatides with long chain-hydroxylated fatty acids (enriched in DRMs) were identified as high-affinity ligands for galectin-4, supporting a model in which galectin-4/sulfatide interaction clusters lipid rafts for apical membrane delivery. |
Retrovirus-mediated RNAi knockdown, detergent-resistant membrane fractionation, post-Golgi vesicle isolation, ligand binding assays |
The Journal of cell biology |
High |
15883199
|
| 2007 |
Galectin-4 binds cholesterol 3-sulfate (which lacks a beta-galactoside moiety), a property unique within the galectin family. Site-directed mutagenesis (R45A) identified Arg45 in the N-terminal CRD as indispensable for cholesterol 3-sulfate recognition. Gel filtration and chemical cross-linking showed that galectin-4 exists as dimers, enhancing avidity for this ligand. Cholesterol 3-sulfate and sulfatide co-exist with galectin-4 in detergent-insoluble fractions of porcine esophagus and intestine, suggesting both are endogenous in vivo ligands. |
Site-directed mutagenesis, gel filtration, chemical cross-linking, detergent-insoluble fractionation |
The Journal of biological chemistry |
High |
17545668
|
| 2013 |
Galectin-4 is tyrosine-phosphorylated by Src family kinases; the C-terminal peptide YVQI is essential for this phosphorylation and binds the SH2 domains of Src and SHP2. Phosphorylation status controls externalization of galectin-4: mutant galectin-4 lacking the C-terminal YVQI peptide is not efficiently externalized. MUC1 from NUGC-4 cells binds galectin-4, and externalization of the MUC1–galectin-4 complex increases under hyperphosphorylated conditions, suggesting galectin-4 acts intracellularly as an adaptor that modulates glycoprotein trafficking. |
Pervanadate treatment, Src co-transfection/phosphorylation assay, SH2 domain binding assay, immunofluorescence, C-terminal deletion mutant transfection |
Glycobiology |
Medium |
24013903
|
| 2014 |
Galectin-4 mediates apical transcytosis of basolateral proteins (exemplified by transferrin receptor, TfR) in epithelial cells lacking the basolateral adaptor AP-1B. Mutation of the N-glycosylation site N727 on TfR or knockdown of galectin-4 blocks TfR transcytosis to apical recycling endosomes and the apical plasma membrane, instead routing TfR to lysosomes for degradation. |
N-glycosylation site mutagenesis, siRNA knockdown, cell fractionation/trafficking assays in RPE, KPT, and AP-1B-knockdown MDCK cells |
Journal of cell science |
High |
25179596
|
| 2012 |
Galectin-4, released by neurons but not oligodendrocytes in vitro, retards oligodendrocyte maturation and inhibits myelination. Treatment of immature oligodendrocytes with galectin-4 causes a subset to revert to a morphologically less complex progenitor stage with increased proliferation. Addition of galectin-4 or anti-galectin-4 antibodies to dorsal root ganglion neuron–oligodendrocyte co-cultures inhibits myelination. Galectin-4-reactive sites are transiently expressed on processes of premyelinating oligodendrocytes (but not neurons), and reduced endogenous galectin-4 release correlates with the onset of myelination. |
In vitro oligodendrocyte treatment, DRG–OLG co-culture myelination assay, immunofluorescence localization, proliferation assays |
Glia |
Medium |
22431161
|
| 2022 |
Galectin-4-deficient (Lgals4-KO) mice show no significant defect in cortical myelin composition, organization, microstructure, or function assessed by electrophysiology and locomotion, indicating that galectin-4 is dispensable for cortical myelination in vivo (negative result). |
Lgals4-KO mouse model, Western blot, immunohistochemistry, in-depth image analysis, in vivo and ex vivo electrophysiology, locomotion assays |
Cells |
Medium |
36359880
|
| 2016 |
Full-length structural model of human galectin-4 was determined using X-ray crystallography and small-/wide-angle X-ray scattering, revealing the structural role of the linker peptide connecting the two CRDs and dynamic characteristics of carbohydrate recognition. The linker peptide confers flexibility and modulates inter-domain communication. |
X-ray crystallography, SAXS/WAXS, molecular dynamics simulations, differential scanning fluorimetry |
Scientific reports |
High |
27642006
|
| 2013 |
Galectin-4 knockdown in HT-29 colorectal cancer cells increases cell proliferation and activates NF-κB and STAT3 signaling with up-regulation of IL-6, demonstrating that galectin-4 suppresses the IL-6/NF-κB/STAT3 signaling axis. This was further confirmed by enhanced xenograft tumor growth in vivo upon shRNA-mediated galectin-4 silencing. |
shRNA knockdown, RT-PCR, qPCR array, Western blotting, immunofluorescence, xenograft assay |
Cellular oncology |
Medium |
23378274
|
| 2013 |
Galectin-4 inhibits migration of pancreatic cancer cells in vitro (scratch assay) and reduces metastasis formation in vivo in a zebrafish model. Galectin-4 accumulates at membrane contact sites between neighboring cells, suggesting it acts as a cell-surface adhesion molecule to prevent tumor cell dissemination. An additional cytosolic function inhibiting migration (mechanism unidentified) is also indicated. |
In vitro scratch assay, zebrafish in vivo metastasis model, immunofluorescence localization |
PloS one |
Medium |
23824659
|
| 2023 |
Extracellular galectin-4 secreted by pancreatic ductal adenocarcinoma cells promotes T-cell apoptosis by binding N-glycosylation residues on CD3ε/δ, mediating immune evasion. In vivo, reduced galectin-4 expression increased T-cell infiltration and prolonged survival in immunocompetent but not immunodeficient RAG1-/- mice, confirming adaptive immune system dependence. |
Orthotopic transplantation, RAG1-/- mouse model, co-culture T-cell apoptosis assay, single-cell RNA-sequencing, binding assay (CD3ε/δ N-glycan) |
Cancer immunology research |
High |
36478037
|
| 2023 |
Galectin-4 on the surface of gastric cancer cells physically interacts with CD44 and c-MET via its carbohydrate-binding domain, maintaining their expression and activation. CRISPR/Cas9-mediated galectin-4 knockout reduced activated c-MET and CD44 levels and attenuated peritoneal metastasis in mice. |
CRISPR/Cas9 knockout, proximity ligation assay, Western blotting, siRNA knockdown, mouse peritoneal metastasis model, immunohistochemistry |
Gastric cancer |
High |
36695981
|
| 2024 |
Galectin-4 antimicrobial activity is primarily mediated by its C-terminal domain (Gal-4C). Gal-4C but not the N-terminal domain (Gal-4N) forms dimers, binds ABO(H) blood group antigens with higher affinity, and displays more potent killing of microbes expressing blood group-like antigens. The full-length Gal-4 also exists as a dimer via Gal-4C dimerization, which functionally renders Gal-4N bivalent, yet Gal-4C retains superior antimicrobial activity. |
Glycan microarray, microbial binding/killing assays, chemical cross-linking (dimer detection), domain-specific recombinant protein assays |
Molecular & cellular proteomics |
Medium |
38490531
|
| 2017 |
Surface-bound galectin-4 on colorectal cancer cells suppresses cell proliferation and chemokine secretion. Neutralization of surface-bound galectin-4 with antibody increases proliferation and upregulates 29 genes in inflammation signaling pathways. Conversely, addition of recombinant galectin-4 to galectin-4-negative colorectal cancer cells increases p27 and decreases cyclin D1 and c-Myc, causing cell cycle arrest and apoptosis. |
Antibody neutralization, recombinant protein treatment, gene expression profiling, Western blotting |
Tumour biology |
Medium |
28345468
|
| 2021 |
Galectin-4 treatment of primary human osteoarthritis chondrocytes induces pro-degradative and pro-inflammatory gene expression (IL-1β, MMP-13) through NF-κB pathway activation (phosphorylation of p65 at Ser536) in a carbohydrate-inhibitable manner. In 3D pellet cultures, galectin-4 causes morphological and biochemical signs of cartilage degradation. |
Primary human chondrocyte culture, recombinant Gal-4 treatment, RT-qPCR, transcriptome analysis, Western blot for p65 phosphorylation, p65 inhibitor experiments, 3D pellet culture |
Histochemistry and cell biology |
Medium |
34846578
|
| 2025 |
Galectin-4 enhances MHC-I surface expression on dendritic cells, promoting CD8+ T-cell responses against tumors and viral infections. Lgals4-KO mice show impaired antigen-MHC-I complex surface expression on DCs and consequently deficient CD8+ T-cell responses, enhanced syngeneic tumor growth, and diminished antiviral CD8+ T-cell responses against LCMV. The defect is DC-intrinsic, not CD8+ T cell-intrinsic. Exogenous Gal-4 administration enhances cancer vaccine and PD-1 blockade efficacy. |
Lgals4-KO mouse model, syngeneic tumor models, LCMV infection, flow cytometry (MHC-I surface expression on DCs), adoptive transfer to distinguish cell-intrinsic defects, cancer vaccine/PD-1 blockade therapeutic experiments |
Molecular therapy |
High |
40589087
|
| 2026 |
Galectin-4 associates with multiple receptor tyrosine kinases (RTKs) including c-MET and EGFR on the gastric cancer cell surface via its carbohydrate recognition domain. In galectin-4 KO cells, tyrosine phosphorylation of proximal RTKs is markedly reduced and c-MET surface expression decreases. Hyperphosphorylation promotes colocalization of galectin-4 with tyrosine-phosphorylated proteins. Surface plasmon resonance showed galectin-4 binds tyrosine-phosphorylated molecules via its CRD; overexpression of B3GALT5 (a glycosyltransferase producing lacto-series glycans) alters PY protein and galectin-4 localization, suggesting competitive regulation of galectin-4 binding by glycosylation vs. tyrosine phosphorylation. |
Antibody array, proximity ligation assay, surface plasmon resonance, galectin-4 KO (CRISPR), B3GALT5 overexpression, Western blotting |
Scientific reports |
Medium |
41991671
|
| 2025 |
Lgals4-KO mice exhibit altered intestinal commensal microbiota, deficient memory formation, and impaired hippocampal LTP in vivo and ex vivo. In vitro, Lgals4-KO neurons show reduced activation of AMPA receptors and CaMKII upon chemically induced LTP. KO mice also display lower hippocampal dendritic spine density, shorter spine length, and increased postsynaptic density area, linking gut galectin-4 (through microbiota modulation) to hippocampal synaptic plasticity. |
Lgals4-KO mouse, 16S rRNA gut microbiota sequencing, behavioral tests, in vivo/ex vivo LTP electrophysiology, immunofluorescence, Western blot (AMPA receptor, CaMKII), RNA-seq, Golgi-Cox staining, electron microscopy |
Biological psychiatry |
Medium |
41101578
|
| 2025 |
Galectin-4 inhibits proteasomal degradation of lactate dehydrogenase A (LDHA) by competitively reducing TRIM28 binding to LDHA, thereby enhancing glycolysis. This promotes HIF-1α-mediated CXCL6 expression, which drives accumulation of PD-L1+ tumor-associated neutrophils and impairs CD8+ T-cell cytotoxicity, conferring resistance to anti-PD-L1/bevacizumab therapy in HCC. |
scRNA-seq, co-culture system, CyTOF, genetic knockdown, pharmacological inhibition, prospective clinical cohort, preclinical HCC mouse models |
Gut |
Medium |
41057233
|
| 2016 |
Galectin-4 overexpression in Rcho-1 rat trophoblast cells inhibits cell enlargement and promotes cell-cell adhesion during differentiation without affecting trophoblast-specific markers or MMP-9 activity. Autophagy inhibitors (3-MA, Bafilomycin A1) prevent the normal downregulation of galectin-4 during trophoblast differentiation, placing autophagy upstream of galectin-4 expression regulation. |
Overexpression in Rcho-1 cells, autophagy inhibitor treatment (3-MA, Bafilomycin A1), Western blot, in vitro differentiation assay |
Scientific reports |
Low |
27572741
|
| 2024 |
B3GALT5 overexpression (introducing lacto-series GSLs with β1,3-linked galactose) reduces galectin-4 colocalization with flotillin-2 in lipid rafts and decreases galectin-4-dependent tumorigenic signaling (reduced activated AKT). GSL synthase inhibitor (PPMP) similarly disrupts galectin-4 raft localization, suggesting that GSL composition of microdomains regulates galectin-4 localization to lipid rafts. |
B3GALT5 overexpression, mass spectrometry glycan profiling, GSL synthase inhibitor treatment, co-localization immunofluorescence (galectin-4/flotillin-2), mouse peritoneal metastasis model |
Glycobiology |
Medium |
39163480
|
| 2023 |
Galectin-4 treatment of M2 macrophages enhances their immunostimulatory gene expression, upregulating antiviral immune response genes, and increases antibody production and antiviral CD4+ T-cell responses (but not CD8+ T-cell responses) against LCMV in vivo. This enhancement is dependent on TLR7 stimulation or viral infection context. |
Recombinant Gal-4 treatment of M1/M2 macrophages, gene expression analysis, TLR7 stimulation, LCMV infection model, in vivo antibody/T-cell response measurement |
Journal of leukocyte biology |
Low |
36822160
|