The Nm23-H1 metastasis suppressor as a translational target.

The Nm23-H1 metastasis suppressor as a translational target.
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DOI:
10.1016/j.ejca.2010.02.042
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发表时间:
2010-05
影响因子:
8.4
通讯作者:
Steeg, Patricia
Steeg, Patricia
中科院分区:
医学1区
文献类型:
--
作者:
Marshall, Jean-Claude;Collins, Joshua;Marino, Natascia;Steeg, Patricia
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nm 23是已经成为超过20个已知转移抑制基因的领域中的第一个。自1988年发现Nm23以来,已将多种机制归因于其活性,包括组氨酸激酶活性、与其他蛋白质结合以调节转移形成以及改变Nm23下游的基因表达。在这里,我们将审查目前的努力,翻译到临床上,包括高剂量的醋酸甲羟孕酮(MPA),这已被证明是上调Nm23的表达,这种转移抑制基因的先前工作。此外,我们将详细介绍Nm23下游的一个新的潜在靶点。LPA 1是一组已知的溶血磷脂酸(LPA)的细胞表面受体之一,其已显示与Nm23表达负相关。特异性LPA1拮抗剂可以通过下调LPA1通路的活性来模拟Nm23的作用,这对于潜在的临床应用将是相当有意义的。
Nm23 was the first of what has become a field of over 20 known metastasis suppressor genes. Since the discovery of Nm23 in 1988, a variety of mechanisms have been attributed to its activity, including a histidine kinase activity, binding of other proteins to regulate metastatic formation, and altered gene expression downstream of Nm23. Here, we will review current efforts to translate the previous work done on this metastasis suppressor gene into the clinic, including high-dose medroxyprogesterone acetate (MPA), which has been shown to upregulate Nm23 expression. In addition, we will detail a new potential target downstream of Nm23. LPA1 is one of a group of known cell surface receptors for lysophosphatidic acid (LPA), which has been shown to be inversely correlated with Nm23 expression. A specific LPA1 antagonist could conceivably mimic the effects of Nm23 by downregulating the activity of the LPA1 pathway, which would be of considerable interest for potential clinical use.
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