JAK/STAT pathway dysregulation in tumors: a Drosophila perspective.
JAK/STAT pathway dysregulation in tumors: a Drosophila perspective.
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DOI：
10.1016/j.semcdb.2014.03.023
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发表时间：
2014-04
影响因子：
7.3
通讯作者：
Bach EA
中科院分区：
文献类型：
--
作者：
Amoyel M;Anderson AM;Bach EA
JAK/STAT通路的持续激活是人类癌症的原因。该途径在果蝇中不太复杂，其失调与该生物体中的几种肿瘤模型有关。在这里，我们讨论模型的转移性上皮和造血肿瘤的因果关系，在果蝇的JAK/STAT信号失调。首先，我们专注于癌症模型中的成虫盘，其中异位表达的JAK/STAT途径配体未配对的下游不同的肿瘤抑制基因已成为一个意想不到的介质的肿瘤转化。我们还讨论了STAT和致癌Ras在上皮转化中的协作。其次，我们研究造血肿瘤，其中导致JAK/STAT信号过度活跃的突变是“苍蝇白血病”的必要和充分条件。我们强调果蝇遗传筛查对了解JAK/STAT途径、其发育作用以及其功能在肿瘤发生过程中如何被利用做出的重要贡献。
Sustained activation of the JAK/STAT pathway is causal to human cancers. This pathway is less complex in Drosophila, and its dysregulation has been linked to several tumor models in this organism. Here, we discuss models of metastatic epithelial and hematopoietic tumors that are causally linked to dysregulation of JAK/STAT signaling in Drosophila. First, we focus on cancer models in imaginal discs where ectopic expression of the JAK/STAT pathway ligand Unpaired downstream of distinct tumor suppressors has emerged as an unexpected mediator of neoplastic transformation. We also discuss the collaboration between STAT and oncogenic Ras in epithelial transformation. Second, we examine hematopoietic tumors, where mutations that cause hyperactive JAK/STAT signaling are necessary and sufficient for “fly leukemia”. We highlight the important contributions that genetic screens in Drosophila have made to understanding the JAK/STAT pathway, its developmental roles, and how its function is co-opted during tumorigenesis.