Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells.
Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells.
复制标题
生长因子诱导的Syndecan-1脱落赋予Glypican-1对癌细胞有丝分裂反应的依赖性。
DOI：
10.1083/jcb.200508010
复制
发表时间：
2005-11-21
期刊：
影响因子：
--
通讯作者：
Lander AD
中科院分区：
文献类型：
--
作者：
Ding K;Lopez-Burks M;Sánchez-Duran JA;Korc M;Lander AD
细胞表面硫酸乙酰肝素蛋白聚糖（HSPG）磷脂酰肌醇蛋白聚糖-1被胰腺癌和乳腺癌细胞上调，其去除使这些细胞对许多生长因子不敏感。我们试图解释为什么细胞表面HSPG多配体蛋白聚糖-1，这也是上调这些细胞，是一个已知的生长因子辅助受体，不补偿磷脂酰肌醇蛋白聚糖-1的损失。我们发现，这些细胞对生长因子FGF 2的初始反应不是磷脂酰肌醇蛋白聚糖依赖性的，但随着时间的推移，它们变得如此，因为FGF 2诱导多配体蛋白聚糖-1的脱落。将多配体蛋白聚糖-1保留在细胞表面上的操作使得长期FGF 2应答不依赖于磷脂酰肌醇蛋白聚糖，而触发多配体蛋白聚糖-1脱落的那些操作使得初始FGF 2应答依赖于磷脂酰肌醇蛋白聚糖。我们进一步表明，syndecan-1脱落是由基质金属蛋白酶-7（MMP-7）介导的，MMP-7通过HSPGs锚定在细胞上，也导致其自身在与syndecan-1胞外域的复合物中释放。这些结果支持脱落多配体蛋白聚糖-1或MMP 7-多配体蛋白聚糖-1复合物在肿瘤进展中的特定作用，并增加了多配体蛋白聚糖和磷脂酰肌醇蛋白聚糖在体内具有不等同功能的证据。
The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated by pancreatic and breast cancer cells, and its removal renders such cells insensitive to many growth factors. We sought to explain why the cell surface HSPG syndecan-1, which is also up-regulated by these cells and is a known growth factor coreceptor, does not compensate for glypican-1 loss. We show that the initial responses of these cells to the growth factor FGF2 are not glypican dependent, but they become so over time as FGF2 induces shedding of syndecan-1. Manipulations that retain syndecan-1 on the cell surface make long-term FGF2 responses glypican independent, whereas those that trigger syndecan-1 shedding make initial FGF2 responses glypican dependent. We further show that syndecan-1 shedding is mediated by matrix metalloproteinase-7 (MMP7), which, being anchored to cells by HSPGs, also causes its own release in a complex with syndecan-1 ectodomains. These results support a specific role for shed syndecan-1 or MMP7–syndecan-1 complexes in tumor progression and add to accumulating evidence that syndecans and glypicans have nonequivalent functions in vivo.
登录
查看更多内容
影响因子：
4.8
作者：
Endo, K;Takino, T;Sato, H
通讯作者：
Sato, H
影响因子：
2.9
作者：
CRABBE, T;WILLENBROCK, F;DOCHERTY, AJP
通讯作者：
DOCHERTY, AJP
影响因子：
4.6
作者：
Desbordes, SC;Sanson, B
通讯作者：
Sanson, B
影响因子：
64.8
作者：
Bellaiche, Y;The, I;Perrimon, N
通讯作者：
Perrimon, N
影响因子：
6.2
作者：
Barbareschi, M;Maisonneuve, P;Doglioni, C
通讯作者：
Doglioni, C