Zhu Fen, Wang Kevin Boyang, Rui Lixin
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Cancers (Basel). 2019 Dec 19;12(1):19. doi: 10.3390/cancers12010019.
Signal transducer and activator of transcription 3 (STAT3) is an important and the most studied transcription factor in the Janus kinase (JAK)/STAT signaling pathway. STAT3 mediates the expression of various genes that play a critical role in many cellular and biological processes, such as cell proliferation, survival, differentiation, migration, angiogenesis, and inflammation. STAT3 and associated JAKs are activated and tightly regulated by a variety of cytokines and growth factors and their receptors in normal immune responses. However, abnormal expression of STAT3 leads to its constitutive activation, which promotes malignant transformation and tumor progression through oncogenic gene expression in numerous human cancers. Human lymphoma is a heterogeneous malignancy of T and B lymphocytes. Constitutive signaling by STAT3 is an oncogenic driver in several types of B-cell lymphoma and most of T-cell lymphomas. Aberrant STAT3 activation can also induce inappropriate expression of genes involved in tumor immune evasion such as . In this review, we focus on the oncogenic role of STAT3 in human lymphoma and highlight potential therapeutic intervention by targeting JAK/STAT3 signaling.
信号转导与转录激活因子3(STAT3)是Janus激酶(JAK)/STAT信号通路中一种重要且研究最多的转录因子。STAT3介导多种基因的表达,这些基因在许多细胞和生物学过程中发挥关键作用,如细胞增殖、存活、分化、迁移、血管生成和炎症。在正常免疫反应中,STAT3和相关的JAKs被多种细胞因子、生长因子及其受体激活并受到严格调控。然而,STAT3的异常表达会导致其组成性激活,通过在众多人类癌症中致癌基因的表达促进恶性转化和肿瘤进展。人类淋巴瘤是T和B淋巴细胞的异质性恶性肿瘤。STAT3的组成性信号传导是几种B细胞淋巴瘤和大多数T细胞淋巴瘤的致癌驱动因素。异常的STAT3激活还可诱导参与肿瘤免疫逃逸的基因的不适当表达,如 。在本综述中,我们聚焦于STAT3在人类淋巴瘤中的致癌作用,并强调通过靶向JAK/STAT3信号传导进行潜在治疗干预。