Basic and translational advances in cancer metastasis: Nm23
Basic and translational advances in cancer metastasis: Nm23
复制标题
DOI：
10.1023/a:1023497924277
复制
发表时间：
2003-02-01
影响因子：
3
通讯作者：
Steeg, PS
中科院分区：
文献类型：
--
作者：
Ouatas, T;Salerno, M;Steeg, PS
肿瘤转移是乳腺癌患者发病率和死亡率的重要因素。为了开发新的抗转移疗法，我们需要了解转移的生物学和生化机制。为了这些努力，我们和其他人研究了转移抑制基因，这些基因可以在不影响原发肿瘤生长的情况下阻止体内转移。第一个确认的转移抑制基因是nm23，也被称为NDP激酶。通过体外实验，nm23过表达导致tgf - β介导的非锚定性定植减少，多种因素介导的侵袭性和移动性降低，分化增强。我们假设Nm23在转移抑制中的作用机制涉及特定受体下游信号转导的减弱。我们假设Nm23的组氨酸蛋白激酶活性是其抑制转移的基础，并确定了候选底物。本文还讨论了基于转移抑制因子的再表达的治疗选择。
Cancer metastasis is a significant contributor to breast cancer patient morbidity and mortality. To develop new anti-metastatic therapies, we need to understand the biological and biochemical mechanisms of metastasis. Toward these efforts, we and others have studied metastasis suppressor genes, which halt metastasis in vivo without affecting primary tumor growth. The first metastasis suppressor gene confirmed was nm23, also known as NDP kinase. Using in vitro assays, nm23 overexpression resulted in reduced anchorage-independent colonization in response to TGF-beta, reduced invasion and motility in response to multiple factors, and increased differentiation. We hypothesize that the mechanism of action of Nm23 in metastasis suppression involves diminished signal transduction, downstream of a particular receptor. We hypothesize that a histidine protein kinase activity of Nm23 underlies its suppression of metastasis, and identify candidate substrates. This review also discusses therapeutic options on the basis of reexpression of metastasis suppressors.