Surface expressed nucleolin is constantly induced in tumor cells to mediate calcium-dependent ligand internalization.
Surface expressed nucleolin is constantly induced in tumor cells to mediate calcium-dependent ligand internalization.
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DOI：
10.1371/journal.pone.0015787
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发表时间：
2010-12-23
期刊：
影响因子：
3.7
通讯作者：
Krust B
中科院分区：
文献类型：
--
作者：
Hovanessian AG;Soundaramourty C;El Khoury D;Nondier I;Svab J;Krust B
核仁素是核仁的主要蛋白质之一，但它也在细胞表面上表达，在细胞表面上作为与肿瘤发生和血管生成有关的各种配体的结合蛋白。越来越多的证据表明，细胞表面表达的核仁素是一个有效和无毒的癌症治疗的战略目标。通过监测核仁素mRNA的表达，并通过测量从细胞表面和细胞核中回收的核仁素蛋白的水平，在这里，我们表明，核仁素在细胞表面的存在依赖于核仁素mRNA的恒定诱导。事实上，RNA转录或翻译的抑制剂阻断表面核仁素的表达，而对细胞核中核仁素的水平没有观察到明显的影响。表面核仁素的估计半衰期小于1小时，而核核仁素的估计半衰期大于8小时。核仁素mRNA诱导在达到汇合的正常成纤维细胞中显著减少，而即使在汇合后的上皮肿瘤细胞中也连续发生，这与它们在没有接触抑制的情况下增殖的能力一致。有趣的是，冷和热休克诱导核仁素mRNA伴随着增强的热休克蛋白70的mRNA表达，从而表明，表面核仁素诱导也发生在响应于环境的侮辱。在细胞表面，核仁素的主要功能之一是通过主动转运机制穿梭特异性的细胞外配体，我们在这里展示了钙依赖性。我们的研究结果表明，表面核仁素的表达是一个早期的代谢事件与肿瘤细胞增殖和应激反应。表面核仁素在肿瘤细胞表面上持续且大量表达的事实使它们成为靶向表面核仁素的抗癌剂的抑制作用的优先靶点。
Nucleolin is one of the major proteins of the nucleolus, but it is also expressed on the cell surface where is serves as a binding protein for variety of ligands implicated in tumorigenesis and angiogenesis. Emerging evidence suggests that the cell-surface expressed nucleolin is a strategic target for an effective and nontoxic cancer therapy. By monitoring the expression of nucleolin mRNA, and by measuring the level of nucleolin protein recovered from the surface and nucleus of cells, here we show that the presence of nucleolin at the cell surface is dependent on the constant induction of nucleolin mRNA. Indeed, inhibitors of RNA transcription or translation block expression of surface nucleolin while no apparent effect is observed on the level of nucleolin in the nucleus. The estimated half-life of surface nucleolin is less than one hour, whereas that of nuclear nucleolin is more than 8 hours. Nucleolin mRNA induction is reduced markedly in normal fibroblasts that reach confluence, while it occurs continuously even in post-confluent epithelial tumor cells consistent with their capacity to proliferate without contact inhibition. Interestingly, cold and heat shock induce nucleolin mRNA concomitantly to enhanced mRNA expression of the heat shock protein 70, thus suggesting that surface nucleolin induction also occurs in response to an environmental insult. At the cell surface, one of the main functions of nucleolin is to shuttle specific extracellular ligands by an active transport mechanism, which we show here to be calcium dependent. Our results demonstrate that the expression of surface nucleolin is an early metabolic event coupled with tumor cell proliferation and stress response. The fact that surface nucleolin is constantly and abundantly expressed on the surface of tumor cells, makes them a preferential target for the inhibitory action of anticancer agents that target surface nucleolin.
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DOI：
10.1111/j.1742-4658.2006.05471.x
发表时间：
2006-10
期刊：
The FEBS journal
影响因子：
--
作者：
Alete DE;Weeks ME;Hovanession AG;Hawadle M;Stoker AW
通讯作者：
Stoker AW
一种新型的受体 - francisella tularensis在单核细胞样THP-1细胞中的配体途径：表面核素与细菌伸长因子TU之间的相互作用。
影响因子：
4.2
作者：
Barel, Monique;Hovanessian, Ara G.;Meibom, Karin;Briand, Jean-Paul;Dupuis, Marion;Charbit, Alain
通讯作者：
Charbit, Alain
影响因子：
3.8
作者：
El Khoury D;Destouches D;Lengagne R;Krust B;Hamma-Kourbali Y;Garcette M;Niro S;Kato M;Briand JP;Courty J;Hovanessian AG;Prévost-Blondel A
通讯作者：
Prévost-Blondel A
影响因子：
3.7
作者：
Di Segni, Ayelet;Farin, Keren;Pinkas-Kramarski, Ronit
通讯作者：
Pinkas-Kramarski, Ronit
影响因子：
4.8
作者：
Hwang, Joonsung;Kalinin, Alexandr;Morasso, Maria I.
通讯作者：
Morasso, Maria I.