TGF-β1 up-regulates paxillin protein expression in malignant astrocytoma cells:: requirement for a fibronectin substrate
TGF-β1 up-regulates paxillin protein expression in malignant astrocytoma cells:: requirement for a fibronectin substrate
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DOI：
10.1038/sj.onc.1204996
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发表时间：
2001-11-29
期刊：
影响因子：
8
通讯作者：
Gladson, CL
中科院分区：
文献类型：
--
作者：
Han, XS;Stewart, JE;Gladson, CL
细胞因子可以影响整合素细胞粘附受体家族成员与细胞外基质之间的相互作用，从而潜在地影响细胞功能并促进恶性星形细胞瘤肿瘤细胞的细胞粘附、生长和迁移。由于恶性星形细胞瘤细胞在体内合成TGF-β 1，我们分析了TGF-β 1对与整合素受体连接相关的信号事件的影响，重点是对桩蛋白（一种磷酸化衔接蛋白）的影响，桩蛋白作为募集到粘着斑的信号分子的支架。TGF-β 1刺激的原代星形胶质细胞和血清饥饿的U-251 MG恶性星形细胞瘤细胞连接到纤连蛋白诱导桩蛋白的水平显着增加（5倍增加，2.0 ng/ml），在剂量和时间依赖性的方式相比，在纤连蛋白上的平板在没有刺激的情况下观察到的水平。在星形细胞瘤细胞中，这导致酪氨酸磷酸化桩蛋白池的增加，尽管它似乎没有改变桩蛋白分子的磷酸化程度。相比之下，在初级星形胶质细胞中，蛋白质水平在磷酸化没有平行增加的情况下上调。TGF-β 1刺激的桩蛋白水平的增加需要纤连蛋白受体的连接，因为当细胞接种在玻连蛋白、胶原蛋白或层粘连蛋白上时，它不会被诱导。在池桩蛋白对TGF-β 1刺激的纤连蛋白铺板星形细胞瘤细胞的增加与翻译的增加，但与桩蛋白mRNA的稳态水平的增加无关。刺激与TGF-β 1的纤连蛋白基板上增加随后的附着和扩散的U-251 MG细胞纤连蛋白，并在较小程度上，玻连蛋白，但不是胶原蛋白。我们的研究结果表明，生理水平的TGF-β 1刺激桩蛋白的表达在翻译水平通过一个过程，需要参与的纤连蛋白受体，并促进附着和扩散的恶性星形细胞瘤细胞的纤连蛋白。
Cytokines can influence the interactions between members of the integrin cell adhesion receptor family and the extracellular matrix thereby potentially affecting cell function and promoting cell adhesion, growth and migration of malignant astrocytoma tumor cells. As malignant astrocytoma cells synthesize TGF-beta1 in vivo, we analysed the effects of TGF-beta1 on signaling events associated with integrin receptor ligation, focusing on the effects on paxillin, a phosphorylated adaptor protein, that acts as a scaffold for signaling molecules recruited to focal adhesions. TGF-beta1 -stimulation of primary astrocytes and serum-starved U-251MG malignant astrocytoma cells attached to fibronectin induced a substantial increase in the levels of paxillin protein (fivefold increase at 2.0 ng/ml) in a dose- and time-dependent manner compared to the levels observed on plating onto fibronectin in the absence of stimulation. In the astrocytoma cells, this resulted in an increase in the pool of tyrosine-phosphorylated paxillin, although it did not appear to alter the extent of phosphorylation of the paxillin molecules. In contrast, in primary astrocytes the protein levels were upregulated in the absence of a parallel increase in phosphorylation. The TGF-beta1-stimulated increase in paxillin levels required ligation of the fibronectin receptor, as it was not induced when the cells were plated onto vitronectin, collagen or laminin. The increase in the pool of paxillin on TGF-beta1 stimulation of the fibronectin-plated astrocytoma cells was associated with an increase in translation, but was not associated with an increase in the steady-state levels of paxillin mRNA. Stimulation with TGF-beta1 on a fibronectin substrate increased subsequent attachment and spreading of U-251MG cells onto fibronectin and, to a lesser extent, vitronectin, but not collagen. Our results indicate that physiologic levels of TGF-beta1 stimulate the expression of paxillin protein at the level of translation through a process that requires engagement of the fibronectin receptor, and promotes attachment and spreading of malignant astrocytoma cells on fibronectin.