Role of galectin-8 as a modulator of cell adhesion and cell growth
Role of galectin-8 as a modulator of cell adhesion and cell growth
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DOI：
10.1023/b:glyc.0000014081.55445.af
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发表时间：
2002-01-01
影响因子：
3
通讯作者：
Ronen, D
中科院分区：
文献类型：
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作者：
Zick, Y;Eisenstein, M;Ronen, D
半凝集素-8属于串联重复型半凝集素家族。它由几个同工异构体组成，每个异构体由两个类似于140个氨基酸的结构域组成，都有一个碳水化合物识别结构域（CRD）。这些结构域由可变长度的“链接肽”连接。人类半乳糖凝集素-8基因覆盖了33 kbp的基因组DNA。它定位于1号染色体（1q42.11），包含11个外显子。该基因通过选择性剪接产生14种不同的转录本，总共编码6种蛋白质。半乳糖凝集素-8和其他半乳糖凝集素一样，是一种分泌蛋白。分泌时，半乳糖凝集素-8作为细胞粘附的生理调节剂。当固定时，它作为一种基质蛋白，与纤维连接蛋白一样，通过连接和聚集细胞表面整合素受体的选择性亚群来促进细胞粘附。半乳糖凝集素-8和整合素之间的复合物形成涉及糖-蛋白相互作用，并触发整合素介导的信号级联反应，如FAK和paxillin的Tyr磷酸化。相反，当作为可溶性配体过量存在时，半乳糖凝集素-8（如纤维连接蛋白）与整合素形成复合物，负向调节细胞粘附。这种机制允许分泌半乳糖凝集素-8发出的局部信号指定可用于细胞粘附和迁移的区域。由于半乳糖凝集素-8对细胞粘附特性的双重作用以及与纤维连接蛋白的关联，它可能被认为是一种新型的基质细胞蛋白。半乳糖凝集素-8的表达水平与某些人类肿瘤呈正相关，前列腺癌是目前研究的最好的例子。由于其调节细胞粘附和细胞生长的能力，过度表达的凝集素可能使这些肿瘤具有一些与生长和转移相关的优势。因此，半乳糖凝集素-8可能在多种生理和病理条件下调节细胞-基质相互作用和调节细胞功能。
Galectin-8 belongs to the family of tandem-repeat type galectins. It consists as several isoforms, each made of two domains of similar to140 amino-acids, both having a carbohydrate recognition domain (CRD). These domains are joined by a 'link peptide' of variable length. The human galectin-8 gene covers 33 kbp of genomic DNA. It is localized on chromosome 1 (1q42.11) and contains 11 exons. The gene produces by alternative splicing 14 different transcripts, altogether encoding 6 proteins. Galectin-8, like other galectins, is a secreted protein. Upon secretion galectin-8 acts as a physiological modulator of cell adhesion. When immobilized, it functions as a matrix protein equipotent to fibronectin in promoting cell adhesion by ligation and clustering of a selective subset of cell surface integrin receptors. Complex formation between galectin-8 and integrins involves sugar-protein interactions and triggers integrin-mediated signaling cascades such as Tyr phosphorylation of FAK and paxillin. In contrast, when present in excess as a soluble ligand, galectin-8 (like fibronectin) forms a complex with integrins that negatively regulates cell adhesion. Such a mechanism allows local signals emitted by secreted galectin-8 to specify territories available for cell adhesion and migration. Due to its dual effects on the adhesive properties of cells and its association with fibronectin, galectin-8 might be considered as a novel type of a matricellular protein. Galectin-8 levels of expression positively correlate with certain human neoplasms, prostate cancer being the best example studied thus far. The overexpressed lectin might give these neoplasms some growth and metastasis related advantages due to its ability to modulate cell adhesion and cellular growth. Hence, galectin-8 may modulate cell-matrix interactions and regulate cellular functions in a variety of physiological and pathological conditions.