文章：

肿瘤中的p21活化激酶

p21-activated kinases in cancer

原文发布日期：2006-06-01

DOI: 10.1038/nrc1892

类型: Review Article

开放获取: 否

要点：

1. p21 activated kinases (Paks) are a family of conserved non-receptor serine/threonine kinases that integrate various signalling pathways that are vital to normal cell survival and function.
2. PAK1 is essential for cell transformation that is induced by various oncogenes, and PAK1 and PAK4 are upregulated and activated in several human tumour types.
3. Paks elicit their biological effects mainly through the activity of interacting proteins or kinase substrates that are involved in multiple cell-regulatory pathways that contribute to cell transformation and tumour-cell invasion.
4. Paks modulate the expression of genes for both survival and metastatic potential through transcriptional modulator substrates and by their association with nuclear chromatin.
5. Demonstration of a role for Paks in tumour development and/or maintenance of invasive phenotypes provides another potential strategy for the development of targeted therapies against Paks and their downstream effectors.
6. Drug-discovery efforts have led to the development of several direct and indirect inhibitors of Paks that could potentially be used as anticancer therapeutics.

要点翻译：

1. p21激活激酶（Paks）是一类保守的非受体丝氨酸/苏氨酸激酶家族，它们整合了多种对正常细胞存活和功能至关重要的信号通路。
2. PAK1对于多种癌基因诱导的细胞转化不可或缺，且PAK1和PAK4在多种人类肿瘤类型中表达上调和激活。
3. Paks主要通过相互作用蛋白或激酶底物的活性发挥其生物学效应，这些底物参与多种细胞调控通路，促进细胞转化和肿瘤细胞侵袭。
4. Paks通过转录调节因子底物以及与核染色质的结合，调控细胞生存和转移潜能相关基因的表达。
5. 证实Paks在肿瘤发展和/或侵袭表型维持中的作用，为开发针对Paks及其下游效应器的靶向疗法提供了另一种潜在策略。
6. 药物研发工作已促成多种直接和间接Paks抑制剂的开发，这些抑制剂可能作为抗癌疗法使用。

英文摘要：

The pivotal role of kinases in signal transduction and cellular regulation has lent them considerable appeal as pharmacological targets across a broad spectrum of cancers. p21-activated kinases (Paks) are serine/threonine kinases that function as downstream nodes for various oncogenic signalling pathways. Paks are well-known regulators of cytoskeletal remodelling and cell motility, but have recently also been shown to promote cell proliferation, regulate apoptosis and accelerate mitotic abnormalities, which results in tumour formation and cell invasiveness. Alterations in Pak expression have been detected in human tumours, which makes them an attractive new therapeutic target.

摘要翻译： 

激酶在信号转导和细胞调控中的关键作用使其成为多种癌症的重要药理靶点。p21活化激酶（Paks）是一类丝氨酸/苏氨酸激酶，作为多种致癌信号通路的下游节点。Paks广为人知的功能是调节细胞骨架重塑和细胞运动，但近期研究还发现其能促进细胞增殖、调控凋亡并加速有丝分裂异常，从而导致肿瘤形成和细胞侵袭。人类肿瘤中已检测到Pak表达的改变，这使其成为极具吸引力的新型治疗靶点。

原文链接：

p21-activated kinases in cancer