O-linked glycosylation modifies CD44 adhesion to hyaluronate in colon carcinoma cells
O-linked glycosylation modifies CD44 adhesion to hyaluronate in colon carcinoma cells
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DOI：
10.1006/bbrc.1996.1475
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发表时间：
1996-10-03
影响因子：
3.1
通讯作者：
Tanabe, KK
中科院分区：
文献类型：
--
作者：
Dasgupta, A;Takahashi, K;Tanabe, KK
CD 44可变剪接模式在正常组织和恶性组织之间不同，因此，在检查CD 44在肿瘤进展中的作用的研究中，CD 44剪接的调节受到了最多的关注。许多研究者已经研究了单个CD 44选择性剪接变体之间的功能差异。然而，特定的CD 44亚型的功能独特地取决于它们表达的细胞类型，从而表明另外的组织特异性机制调节CD 44功能。目前的研究表明，结肠癌细胞修饰的CD 44与O-连接的糖基基团，和这种糖基化的阻断增强其CD 44介导的粘附透明质酸。这种增强主要归因于CD 44 H（CD 44 s），而不是高分子量CD 44变体。使用定点突变的CD 44 H cDNA转染子表明，CD 44 O-连接的糖基化调节透明质酸和CD 44的B环结构域之间的相互作用。糖基化对结肠癌细胞中CD 44功能的影响是特定于O-连接糖的存在;抑制N-连接糖基化对CDU功能的影响最小。这些发现表明，O-连接的糖基化可能是一样重要的选择性剪接的调节CD 44功能和广谱的生物过程归因于它，包括正常的发展，肿瘤转移，淋巴细胞功能。(C)出版社：Academic Press，Inc.
CD44 alternative splicing patterns differ between normal and malignant tissue, and accordingly, modulation of CD44 splicing has received the most attention in studies that have examined the role of CD44 in tumor progression. Many investigators have examined functional differences between individual CD44 alternative splice variants. However, specific CD44 isoforms function uniquely depending on the type of cell on which they are expressed, thereby suggesting that additional tissue-specific mechanisms regulate CD44 function. To the present study we have demonstrated that colon carcinoma cells modify CD44 with O-linked glycosyl groups, and blockade of this glycosylation enhances their CD44-mediated adhesion to hyaluronate. This enhancement is attributable principally to CD44H (CD44s) rather than high molecular weight CD44 variants. Use of site-directed mutant CD44H cDNA transfectants demonstrated that CD44 O-linked glycosylation modulates interaction between hyaluronate and the B loop domain of CD44. The influence of glycosylation on CD44 function in colon carcinoma cells is specific to the presence of O-linked sugars; inhibition of N-linked glycosylation had minimal influence on CDU function. These findings indicate that O-linked glycosylation may be as important as alternative splicing in the regulation of CD44 function and the broad spectrum of biological processes attributed to it, including normal development, tumor metastases, and lymphocyte function. (C) 1996 Academic Press, Inc.