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信号转导及转录激活因子3(STAT3)的作用及其在血液系统恶性肿瘤中的靶向抑制

The Role of Signal Transducer and Activator of Transcription 3 (STAT3) and Its Targeted Inhibition in Hematological Malignancies.

作者信息

Arora Loukik, Kumar Alan Prem, Arfuso Frank, Chng Wee Joo, Sethi Gautam

机构信息

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.

Cancer Science Institute of Singapore, Centre for Translational Medicine, 14 Medical Drive, #11-01M, Singapore 117599, Singapore.

出版信息

Cancers (Basel). 2018 Sep 13;10(9):327. doi: 10.3390/cancers10090327.

Abstract

Signal transducer and activator of transcription 3 (STAT3), a member of the STAT protein family, can be phosphorylated by receptor-associated Janus kinases (JAKs) in response to stimulation by cytokines and growth factors. It forms homo- or heterodimers that can translocate to the cell nucleus where they act as transcription activators. Constitutive activation of STAT3 has been found to be associated with initiation and progression of various cancers. It can exert proliferative as well as anti-apoptotic effects. This review focuses on the role of STAT3 in pathogenesis i.e., proliferation, differentiation, migration, and apoptosis of hematological malignancies viz. leukemia, lymphoma and myeloma, and briefly highlights the potential therapeutic approaches developed against STAT3 activation pathway.

摘要

信号转导及转录激活因子3(STAT3)是STAT蛋白家族的成员之一,可在细胞因子和生长因子的刺激下被受体相关的Janus激酶(JAKs)磷酸化。它形成同源或异源二聚体,能够转运至细胞核,在细胞核中作为转录激活因子发挥作用。已发现STAT3的组成性激活与多种癌症的发生和发展有关。它可发挥增殖以及抗凋亡作用。本综述重点关注STAT3在血液系统恶性肿瘤(即白血病、淋巴瘤和骨髓瘤)的发病机制(即增殖、分化、迁移和凋亡)中的作用,并简要介绍针对STAT3激活途径开发的潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f923/6162647/7688b1dc8356/cancers-10-00327-g001.jpg

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