Galectin-4 in normal tissues and cancer
Galectin-4 in normal tissues and cancer
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DOI：
10.1023/b:glyc.0000025819.54723.a0
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发表时间：
2003-01-01
影响因子：
3
通讯作者：
Leffler, H
中科院分区：
文献类型：
--
作者：
Huflejt, ME;Leffler, H
半乳糖凝集素-4属于半乳糖凝集素的亚家族，由同一肽链内的两个碳水化合物识别结构域组成。这两个结构域具有所有保守的半乳糖凝集素特征氨基酸，但它们的整体序列仅约40%相同。这两个结构域与乳糖结合的亲和力与其他半乳糖凝集素相似，但它们各自对其他二糖和更大的乳糖的偏好明显不同。因此，半乳糖凝集素-4具有天然交联剂的性质，但在修饰的意义上，因为每个结构域偏好不同的配体子集。与其他半乳糖凝集素类似，半乳糖凝集素-4作为胞质蛋白合成，但可以外化。在发育期间和在成人正常组织中，半乳糖凝集素-4仅在从舌到大肠的消化道中表达。它通常存在于相对不溶性的复合物中，作为微绒毛膜中粘附连接或脂筏的组分，并已提出稳定这些结构。然而，在其他组织（包括乳腺癌和肝癌）的癌症中，可以诱导半乳糖凝集素-4的强表达。在一组人上皮癌细胞系中，半乳糖凝集素-4在形成高度分化的极化单层的细胞中过表达并可溶，但在分化程度较低的细胞中不存在。在培养的细胞中，细胞内的半乳糖凝集素-4可以促进对营养饥饿的抵抗，而作为细胞外蛋白，它可以介导细胞粘附。由于它在乳腺癌和其他癌症中的独特诱导作用，它可能是一个有价值的诊断标志物和开发抑制性碳水化合物药物的靶点。
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.