Gangliosides inhibit urokinase-type plasminogen activator (uPA)-dependent squamous carcinoma cell migration by preventing uPA receptor/alphabeta integrin/epidermal growth factor receptor interactions.
Gangliosides inhibit urokinase-type plasminogen activator (uPA)-dependent squamous carcinoma cell migration by preventing uPA receptor/alphabeta integrin/epidermal growth factor receptor interactions.
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DOI：
10.1111/j.0022-202x.2005.23669.x
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发表时间：
2005-04
期刊：
影响因子：
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通讯作者：
Xiao-Qi Wang;P. Sun;A. Paller
中科院分区：
文献类型：
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作者：
Xiao-Qi Wang;P. Sun;A. Paller
尿激酶型纤溶酶原激活物（uPA）受体（uPAR）与整合素的相互作用在细胞粘附和迁移调控中起着至关重要的作用。然而，调控uPAR和整合素相互作用的分子事件尚不清楚。神经节苷脂被认为通过抑制α (5) β(1)整合素和表皮生长因子受体（EGFR）信号传导来调节上皮细胞的粘附和迁移。我们在这里报道神经节苷脂NeuAcalpha2—>galbeta1—>3GalNAcbeta1—>4(NeuAcalpha2—>8NeuAcalpha2—>3)Galbeta1—>4Glcbeta1-Cer （GT1b）或NeuAcalpha2—>3Galbeta1—>4Glcbeta1-Cer （GM3）的表达增加分别通过阻止uPAR与α (5) β(1)整合素或uPAR/ α (5) β(1)整合素与EGFR的关联来抑制upa依赖性细胞迁移。结果，upa依赖性局灶黏着激酶（FAK）和整合素介导的EGFR信号被抑制。两种神经节苷脂均抑制uPAR信号刺激的迁移；然而，GM3通过阻断整合素和EGFR之间的串扰来抑制upa诱导的EGFR磷酸化，而GT1b通过阻止整合素α (5) β的激活来抑制upa诱导的FAK和EGFR激活(1)。
The interaction of the urokinase-type plasminogen activator (uPA) receptor (uPAR) with integrins plays a critical role in the regulation of cell adhesion and migration. However, the molecular events underlying the modulation of the interaction of uPAR and integrin are poorly understood. Gangliosides are thought to regulate epithelial cell adhesion and migration by inhibiting alpha(5)beta(1) integrin and epidermal growth factor receptor (EGFR) signaling. We report here that increases in the expression of ganglioside NeuAcalpha2-->3Galbeta1-->3GalNAcbeta1-->4(NeuAcalpha2-->8NeuAcalpha2-->3)Galbeta1-->4Glcbeta1-Cer (GT1b) or NeuAcalpha2-->3Galbeta1-->4Glcbeta1-Cer (GM3) inhibit uPA-dependent cell migration by preventing the association of uPAR with alpha(5)beta(1) integrin or uPAR/alpha(5)beta(1) integrin with the EGFR, respectively. As a result, uPA-dependent focal adhesion kinase (FAK) and integrin-mediated EGFR signaling are suppressed. Both gangliosides inhibit uPAR signaling-stimulated migration; however, GM3 inhibits uPA-induced EGFR phosphorylation by blocking the crosstalk between integrin and EGFR, whereas GT1b suppresses both uPA-induced FAK and EGFR activation by preventing the activation of integrin alpha(5)beta(1).