文章：

JNK和p38 MAPK通路在癌症发展中的信号整合

Signal integration by JNK and p38 MAPK pathways in cancer development

原文发布日期：2009-08-01

DOI: 10.1038/nrc2694

类型: Review Article

开放获取: 否

要点：

1. Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinases (MAPKs) have important roles in the signalling mechanisms that orchestrate cellular responses to many types of stresses, but also control the proliferation, differentiation, survival and migration of specific cell types.
2. JNKs and p38 MAPKs can exert antagonistic effects on cell proliferation and survival, which depend on cell type-specific differences, as well as on the intensity and duration of the signal and the crosstalk between other signalling pathways.
3. Crosstalk between the JNK and p38 MAPK pathways is emerging as an important regulatory mechanism in many cellular responses.
4. The JNK and p38 MAPK pathways regulate the activity and expression of key inflammatory mediators, including cytokines and proteases, which may function as potent cancer promoters.
5. The specific role of individual JNK and p38 MAPK family members in particular cellular processes in vivo has been addressed by gene-targeting experiments in mice. Genetically engineered mouse models have confirmed the importance of these pathways for tumorigenesis in various organs.
6. The expression or activity of JNK and p38 MAPK pathway components is often altered in human tumours and cancer cell lines. Given the many tumorigenesis-related functions that these kinases can control, both in the cancer cell and in the tumour microenvironment, it is important to carefully consider the type of tumour before attempting to modulate these pathways for cancer therapy.

要点翻译：

1. Jun N末端激酶（JNKs）和p38丝裂原活化蛋白激酶（MAPKs）不仅在协调细胞对多种应激反应的信号机制中发挥重要作用，还调控特定细胞类型的增殖、分化、存活与迁移。
2. JNKs与p38 MAPKs能对细胞增殖和存活产生拮抗效应，这种效应取决于细胞类型特异性差异、信号强度与持续时间以及与其他信号通路的交互作用。
3. JNK与p38 MAPK通路间的交叉调控正逐渐成为许多细胞反应中的重要调节机制。
4. JNK和p38 MAPK通路调控包括细胞因子和蛋白酶在内的关键炎症介质活性与表达，这些介质可能作为强效癌症促进因子发挥作用。
5. 通过小鼠基因靶向实验，研究人员已揭示了特定JNK和p38 MAPK家族成员在体内特定细胞过程中的具体功能。基因工程小鼠模型证实了这些通路对多种器官肿瘤发生的重要性。
6. 在人类肿瘤和癌细胞系中，JNK与p38 MAPK通路组分的表达或活性常发生改变。鉴于这些激酶可同时调控癌细胞和肿瘤微环境中多种与肿瘤发生相关的功能，在尝试通过调控这些通路进行癌症治疗前，必须审慎考虑肿瘤类型。

英文摘要：

Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) family members function in a cell context-specific and cell type-specific manner to integrate signals that affect proliferation, differentiation, survival and migration. Consistent with the importance of these events in tumorigenesis, JNK and p38 MAPK signalling is associated with cancers in humans and mice. Studies in mouse models have been essential to better understand how these MAPKs control cancer development, and these models are expected to provide new strategies for the design of improved therapeutic approaches. In this Review we highlight the recent progress made in defining the functions of the JNK and p38 MAPK pathways in different cancers.

摘要翻译： 

Jun N末端激酶（JNK）和p38丝裂原活化蛋白激酶（MAPK）家族成员以细胞特异性和细胞类型特异性的方式发挥作用，整合影响增殖、分化、存活和迁移的信号。鉴于这些事件在肿瘤发生中的重要性，JNK和p38 MAPK信号通路与人类和小鼠的癌症相关。小鼠模型研究对于更好地理解这些MAPKs如何控制癌症发展至关重要，这些模型有望为改进治疗策略的设计提供新方法。在本综述中，我们强调了在定义JNK和p38 MAPK通路在不同癌症中功能方面的最新进展。

原文链接：

Signal integration by JNK and p38 MAPK pathways in cancer development