The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human mammary carcinoma cells.

The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human mammary carcinoma cells.
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DOI:
10.1083/jcb.200404171
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发表时间:
2004-10-11
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Rapraeger AC
Rapraeger AC
中科院分区:
其他
文献类型:
--
作者:
Beauvais DM;Burbach BJ;Rapraeger AC

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αvβ3 整合素参与细胞形态发生、生长因子信号传导和细胞存活。整合素的激活是这些过程的核心,并受到特定 ECM 成分的影响,这些成分与整合素和多聚糖结合。本文证明 αvβ3 整合素和 syndecan-1 (S1) 在功能上是耦合的。整合素依赖于多聚糖被激活并介导 MDA-MB-231 和 MDA-MB-435 人乳腺癌细胞在玻连蛋白或 S1 特异性抗体上扩散所需的信号。多聚糖与 αvβ3 的偶联需要 S1 胞外域 (ED),因为糖基磷脂酰肌醇连接的 S1ED 的异位表达增强了 αvβ3 对玻连蛋白的识别;针对该结构域的治疗,包括与重组 S1ED 蛋白或抗 S1ED 抗体竞争、S1ED 突变或小干扰 RNA 下调 S1 表达,会破坏 αvβ3 依赖性细胞扩散和迁移。因此,S1 可能是许多依赖于激活的 αvβ3 整合素的细胞行为的关键调节因子。
The αvβ3 integrin participates in cell morphogenesis, growth factor signaling, and cell survival. Activation of the integrin is central to these processes and is influenced by specific ECM components, which engage both integrins and syndecans. This paper demonstrates that the αvβ3 integrin and syndecan-1 (S1) are functionally coupled. The integrin is dependent on the syndecan to become activated and to mediate signals required for MDA-MB-231 and MDA-MB-435 human mammary carcinoma cell spreading on vitronectin or S1-specific antibody. Coupling of the syndecan to αvβ3 requires the S1 ectodomain (ED), as ectopic expression of glycosylphosphatidylinositol-linked S1ED enhances αvβ3 recognition of vitronectin; and treatments that target this domain, including competition with recombinant S1ED protein or anti-S1ED antibodies, mutation of the S1ED, or down-regulation of S1 expression by small-interfering RNAs, disrupt αvβ3-dependent cell spreading and migration. Thus, S1 is likely to be a critical regulator of many cellular behaviors that depend on activated αvβ3 integrins.
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