Laboratory of Transcription Regulation, Department of Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St, PL 02-093, Warsaw, Poland.
Adv Exp Med Biol. 2020;1202:203-222. doi: 10.1007/978-3-030-30651-9_10.
STAT (signal transducers and activators of transcription) are latent cytoplasmic transcription factors that function as downstream effectors of cytokine and growth factor receptor signaling. The canonical JAK/STAT signaling pathway involves the activation of Janus kinases (JAK) or growth factors receptor kinases, phosphorylation of STAT proteins, their dimerization and translocation into the nucleus where STATs act as transcription factors with pleiotropic downstream effects. STAT signaling is tightly controlled with restricted kinetics due to action of its negative regulators. While STAT1 is believed to play an important role in growth arrest and apoptosis, and to act as a tumor suppressor, STAT3 and 5 are involved in promoting cell cycle progression, cellular transformation, and preventing apoptosis. Aberrant activation of STATs, in particular STAT3 and STAT5, have been found in a large number of human tumors, including gliomas and may contribute to oncogenesis. In this chapter, we have (1) summarized the mechanisms of STAT activation in normal and malignant signaling; (2) discussed evidence for the critical role of constitutively activated STAT3 and STAT5 in glioma pathobiology; (3) disclosed molecular and pharmacological strategies to interfere with STAT signaling for potential therapeutic intervention in gliomas.
STAT（信号转导子和转录激活子）是潜在的细胞质转录因子，作为细胞因子和生长因子受体信号转导的下游效应子发挥作用。典型的 JAK/STAT 信号通路涉及 Janus 激酶（JAK）或生长因子受体激酶的激活、STAT 蛋白的磷酸化、它们的二聚化和易位到细胞核内，在细胞核内 STAT 作为转录因子具有多效性的下游效应。由于其负调节剂的作用，STAT 信号受到严格控制，动力学受限。虽然 STAT1 被认为在生长停滞和细胞凋亡中发挥重要作用，并作为肿瘤抑制因子，但 STAT3 和 STAT5 参与促进细胞周期进程、细胞转化和防止细胞凋亡。在大量人类肿瘤中发现了 STAT 的异常激活，特别是 STAT3 和 STAT5，这可能有助于肿瘤发生。在本章中，我们（1）总结了正常和恶性信号中 STAT 激活的机制；（2）讨论了持续激活的 STAT3 和 STAT5 在神经胶质瘤发病机制中的关键作用的证据；（3）揭示了干扰 STAT 信号的分子和药理学策略，以期在神经胶质瘤中进行潜在的治疗干预。
