Evolvable signaling networks of receptor tyrosine kinases: relevance of robustness to malignancy and to cancer therapy.
Evolvable signaling networks of receptor tyrosine kinases: relevance of robustness to malignancy and to cancer therapy.
复制标题
受体酪氨酸激酶的可发展信号网络：鲁棒性与恶性肿瘤和癌症治疗的相关性。
DOI：
10.1038/msb4100195
复制
发表时间：
2007
影响因子：
9.9
通讯作者：
Yarden, Yosef
中科院分区：
文献类型：
--
作者：
Amit, Ido;Wides, Ron;Yarden, Yosef
通过基因复制，强大的生物信号网络从简单、相对脆弱的级联进化而来。分层配置、分支和模块化等架构特征以及功能特性（例如，反馈控制电路）在面对内部和外部扰动时能够实现故障安全性能。这些普遍特征在此使用受体酪氨酸激酶（RTK）家族举例说明。RTK模块在人类恶性肿瘤中大量突变和过表达，其信号传导的药物拦截有效地延缓了特定肿瘤的生长。治疗诱导的RTK信号通路的拦截和耐药的共同演变分别被认为是鲁棒网络的脆弱性和可塑性的表现。我们提出的系统观点将病理学视为生物稳健性的劫持者，并提供了识别脆弱枢纽的方法，以及克服耐药性的策略。
Robust biological signaling networks evolved, through gene duplications, from simple, relatively fragile cascades. Architectural features such as layered configuration, branching and modularity, as well as functional characteristics (e.g., feedback control circuits), enable fail-safe performance in the face of internal and external perturbations. These universal features are exemplified here using the receptor tyrosine kinase (RTK) family. The RTK module is richly mutated and overexpressed in human malignancies, and pharmaceutical interception of its signaling effectively retards growth of specific tumors. Therapy-induced interception of RTK-signaling pathways and the common evolvement of drug resistance are respectively considered here as manifestations of fragility and plasticity of robust networks. The systems perspective we present views pathologies as hijackers of biological robustness and offers ways for identifying fragile hubs, as well as strategies to overcome drug resistance.