Disease relevance of LGALS4

• These findings suggest that SB1a and CEA in the patches on the cell surface of human colon adenocarcinoma cells could be biologically important ligands for galectin-4 [1].
• Cloning and expression of the mRNA of human galectin-4, an S-type lectin down-regulated in colorectal cancer [2].
• The assumed role of galectin-4 as a microvillar raft stabilizer/organizer and as a malignancy-associated factor in hepatocellular and gastrointestinal carcinomas called for further refinement of its binding specificity [3].

High impact information on LGALS4

• The most up-regulated genes in BE compared with squamous epithelium were trefoil factors, annexin A10, and galectin-4 [4].
• Here, we have identified galectin-4 as one of the major components of detergent-resistant membranes (DRMs) isolated from HT-29 5M12 cells [5].
• The functional role of galectin-4 in polarized trafficking in HT-29 5M12 cells was studied by using a retrovirus-mediated RNA interference [5].
• In addition, IGFBP-1 and Gal-4 mRNAs were also induced by reducing the serum concentration to 0.1% [6].
• Galectin-4 binds to sulfated glycosphingolipids and carcinoembryonic antigen in patches on the cell surface of human colon adenocarcinoma cells [1].

Biological context of LGALS4

• The localization of galectin-4 suggests a role in cell adhesion which is also supported by the ability of immobilized recombinant galectin-4 to stimulate adhesion of T84 cells [7].
• Others, like human cell death protein, TRAIL, and galectin-4 participate in the regulation of apoptosis [8].

Anatomical context of LGALS4

• Galectin-4, a member of the galectin family, is expressed in the epithelium of the alimentary tract [1].
• Cloning and sequencing of one, a 36-kDa protein, identified it as the human homolog of galectin-4, a protein containing two carbohydrate binding domains and previously found only in the epithelial cells of the rat and porcine alimentary tract [7].
• Among five cell lines derived from colon carcinoma, only two (HT29 and LS174T) expressed galectin-4 mRNA [2].
• During development and in adult normal tissues, galectin-4 is expressed only in the alimentary tract, from the tongue to the large intestine [9].
• In cultured cells, intracellular galectin-4 may promote resistance to nutrient starvation, whereas--as an extracellular protein--it can mediate cell adhesion [9].

Associations of LGALS4 with chemical compounds

• In contrast, galectin-4 had quite weak affinity to lactose, type 1, and type 2 (K(d) congruent with 8 x 10(-4) M) [10].
• Glycolipids, rather than cholesterol, together with the divalent lectin galectin-4, define these rafts, which are stable and probably quite large [11].
• Thus, microvillar rafts are stable rather than transient/dynamic, and their core components include glycolipids and the divalent lectin galectin-4, which together can be isolated as "superrafts", i.e., membrane microdomains resisting solubilization with Triton X-100 at physiological temperature [12].
• The site-directed mutated galectin-4-R45A had diminished binding ability toward cholesterol 3-sulfate, suggesting that Arg(45) of galectin-4 is indispensable for cholesterol 3-sulfate recognition [13].

Other interactions of LGALS4

• In addition to commonly studied galectins-1 and -3, tandem-repeat-type galectins could be detected, i.e., galectin-8 in six from 15 cases and galectin-4 in one of 15 cases [14].
• Signals for galectin-9, the third known human tandem-repeat-type galectin besides -4 and -8, appeared in colorectal carcinoma cell lines with a frequency similar to that of galectin-4 but with inter-line differences [15].
• Three of the 48 antigens showed a differential pattern of mRNA expression, with NY-CO-27 (galectin-4) expressed primarily in gastrointestinal tract, and NY-CO-37 and -38 showing a pattern of tissue-specific isoforms [16].
• The resultant knockdown of HIP/RPL29 expression induced cellular differentiation, as shown by the increased expression of two known markers of differentiation in LS174T cells, galectin-4 and mucin-2 [17].

Analytical, diagnostic and therapeutic context of LGALS4

• In this study, we found that galectin-4 binds to glycosphingolipids carrying 3-O-sulfated Gal residues, such as SB1a, SM3, SM4s, SB2, SM2a, and GM1, but not to glycosphingolipids with 3-O-sialylated Gal, such as sLc4Cer, snLc4Cer, GM3, GM2, and GM4, using both an enzyme-linked immunosorbent assay and a surface plasmon resonance assay [1].

References