PDF(Pubmed)
Abstract：
Through a comprehensive review and in silico analysis of reported data on STAT-linked diseases, we analysed the communication pathways and interactome of the seven STATs in major cancer categories and proposed rational targeting approaches for therapeutic intervention to disrupt critical pathways and addictions to hyperactive JAK/STAT in neoplastic states. Although all STATs follow a similar molecular activation pathway, STAT1, STAT2, STAT4 and STAT6 exert specific biological profiles associated with a more restricted pattern of activation by cytokines. STAT3 and STAT5A as well as STAT5B have pleiotropic roles in the body and can act as critical oncogenes that promote many processes involved in cancer development. STAT1, STAT3 and STAT5 also possess tumour suppressive action in certain mutational and cancer type context. Here, we demonstrated member-specific STAT activity in major cancer types. Through systems biology approaches, we found surprising roles for EGFR family members, sex steroid hormone receptor ESR1 interplay with oncogenic STAT function and proposed new drug targeting approaches of oncogenic STAT pathway addiction.
摘要：
通过对与STAT有关的疾病的报告数据进行全面审查和计算机模拟分析，我们分析了7种STATs在主要癌症类别中的通讯通路和相互作用组,并提出了治疗干预的合理靶向方法,以破坏肿瘤状态中的JAK/STAT的关键通路和成瘾性.尽管所有STATs都遵循相似的分子激活途径，STAT1、STAT2、STAT4和STAT6发挥与细胞因子激活的更受限模式相关的特定生物学特征。STAT3和STAT5A以及STAT5B在体内具有多效性作用，并且可以作为促进癌症发展中涉及的许多过程的关键癌基因。STAT1、STAT3和STAT5在某些突变和癌症类型背景下也具有肿瘤抑制作用。这里,我们证明了主要癌症类型的成员特异性STAT活性。通过系统生物学方法，我们发现EGFR家族成员的作用令人惊讶，性类固醇激素受体ESR1与致癌STAT功能相互作用，并提出了致癌STAT途径成瘾的新药物靶向方法。
