Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Int J Mol Sci. 2018 Dec 14;19(12):4056. doi: 10.3390/ijms19124056.
Over the past three-decades, Janus kinase (Jak) and signal transducer and activator of transcription (STAT) signaling has emerged as a paradigm to understand the involvement of signal transduction in development and disease pathology. At the molecular level, cytokines and interleukins steer Jak/STAT signaling to transcriptional regulation of target genes, which are involved in cell differentiation, migration, and proliferation. Jak/STAT signaling is involved in various types of blood cell disorders and cancers in humans, and its activation is associated with carcinomas that are more invasive or likely to become metastatic. Despite immense information regarding Jak/STAT regulation, the signaling network has numerous missing links, which is slowing the progress towards developing drug therapies. In mammals, many components act in this cascade, with substantial cross-talk with other signaling pathways. In , there are fewer pathway components, which has enabled significant discoveries regarding well-conserved regulatory mechanisms. Work across species illustrates the relevance of these regulators in humans. In this review, we showcase fundamental Jak/STAT regulation mechanisms in blood cells, stem cells, and cell motility. We examine the functional relevance of key conserved regulators from to human cancer stem cells and metastasis. Finally, we spotlight less characterized regulators of Jak/STAT signaling, which stand as promising candidates to be investigated in cancer biology. These comparisons illustrate the value of using as a model for uncovering the roles of Jak/STAT signaling and the molecular means by which the pathway is controlled.
在过去的三十年中，Janus 激酶（Jak）和信号转导子和转录激活子（STAT）信号转导已成为理解信号转导在发育和疾病病理学中的作用的范例。在分子水平上，细胞因子和白细胞介素引导 Jak/STAT 信号转导，从而对靶基因进行转录调控，这些靶基因参与细胞分化、迁移和增殖。Jak/STAT 信号转导参与了人类各种类型的血细胞疾病和癌症，其激活与侵袭性更强或更有可能转移的癌有关。尽管关于 Jak/STAT 调节有大量信息，但信号网络存在许多缺失的环节，这减缓了开发药物治疗的进展。在哺乳动物中，许多成分在这个级联中起作用，与其他信号通路有大量的交叉对话。在 中，有较少的途径成分，这使得关于保守调控机制的重要发现成为可能。跨物种的工作说明了这些调节剂在人类中的相关性。在这篇综述中，我们展示了血细胞、干细胞和细胞运动中 Jak/STAT 调节的基本机制。我们检查了从 到人类癌症干细胞和转移中关键保守调节剂的功能相关性。最后，我们突出了 Jak/STAT 信号转导中较少表征的调节剂，它们是癌症生物学中值得研究的有希望的候选者。这些比较说明了使用 作为揭示 Jak/STAT 信号转导作用和控制途径的分子手段的模型的价值。
