Galectin-4 in normal tissues and cancer.
Galectin-4 belongs to a subfamily of galectins composed of two carbohydrate recognition domains within the same peptide chain. The two domains have all the conserved galectin signature amino acids, but their overall sequences are only approximately 40% identical. Both domains bind lactose with a similar affinity as other galectins, but their respective preferences for other disaccharides, and larger saccharides, are distinctly different. Thus galectin-4 has a property of a natural cross-linker, but in a modified sense since each domain prefers a different subset of ligands. Similarly to other galectins, galectin-4 is synthesized as a cytosolic protein, but can be externalized. During development and in adult normal tissues, galectin-4 is expressed only in the alimentary tract, from the tongue to the large intestine. It is often found in relatively insoluble complexes, as a component of either adherens junctions or lipid rafts in the microvillus membrane, and it has been proposed to stabilize these structures. Strong expression of galectin-4 can be induced, however, in cancers from other tissues including breast and liver. Within a collection of human epithelial cancer cell lines, galectin-4 is overexpressed and soluble in those forming highly differentiated polarized monolayers, but absent in less differentiated ones. In cultured cells, intracellular galectin-4 may promote resistance to nutrient starvation, whereas--as an extracellular protein--it can mediate cell adhesion. Because of its distinct induction in breast and other cancers, it may be a valuable diagnostic marker and target for the development of inhibitory carbohydrate-based drugs.
Huflejt
Margaret E
ME
Sidney Kimmel Cancer Center, 10835 Altman Row, San Diego, CA 92121, USA. mhuflejt@skcc.org
Leffler
Hakon
H
D001693:Biological Transport, Active / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000503:physiopathology*; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D037541:Galectin 4 / Q000235:genetics / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000503:physiopathology*; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D014408:Biomarkers, Tumor; D037541:Galectin 4; D011134:Polysaccharides