STAT3 and its targeting inhibitors in osteosarcoma.
STAT3 and its targeting inhibitors in osteosarcoma.
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STAT3及其靶向抑制剂在骨肉瘤中的作用
DOI：
10.1111/cpr.12974
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发表时间：
2021-03
影响因子：
8.5
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Liu Y;Liao S;Bennett S;Tang H;Song D;Wood D;Zhan X;Xu J
信号转导子和转录激活子3（STAT 3）是参与调节细胞生长、分化和存活的七个STAT家族成员之一。STAT蛋白在真核生物中是保守的，并且对于胚胎发生、免疫、造血和细胞迁移的生物学功能是重要的。STAT 3广泛表达并以非活性形式定位于细胞质中。STAT 3通过一系列信号传导途径，包括来自IL-6家族的细胞因子和生长因子（如EGF和PDGF），通过酪氨酸磷酸化快速瞬时激活。STAT 3激活和随后的二聚体形成启动STAT 3的核转位以调节靶基因转录。已经鉴定了四种STAT 3亚型，它们具有不同的生物学功能。STAT 3被认为是一种原癌基因，STAT 3的组成性激活与多种癌症的发展有关，包括多发性骨髓瘤、白血病和淋巴瘤。本文就STAT 3与骨肉瘤（osteosarcoma，OS）的关系作一综述。值得注意的是，STAT 3过表达并与OS的不良预后相关。OS中STAT 3的组成性激活似乎上调靶癌基因的表达，导致OS细胞转化、增殖、肿瘤形成、侵袭、转移、免疫逃避和耐药性。总之，STAT 3是癌症治疗的靶点，并且STAT 3抑制剂代表用于治疗OS的潜在治疗候选物。信号转导子和转录激活子3（STAT 3）是STAT蛋白家族的成员，对于真核细胞至关重要。我们回顾了STAT 3及其亚型的分子结构和功能，突出了基因转录调控的信号通路。提供了STAT 3在癌症（如骨肉瘤）中的重要评价，强调了靶向STAT 3及其抑制剂的潜在治疗方法。
Signal transducer and activator of transcription 3 (STAT3) is one of seven STAT family members involved with the regulation of cellular growth, differentiation and survival. STAT proteins are conserved among eukaryotes and are important for biological functions of embryogenesis, immunity, haematopoiesis and cell migration. STAT3 is widely expressed and located in the cytoplasm in an inactive form. STAT3 is rapidly and transiently activated by tyrosine phosphorylation by a range of signalling pathways, including cytokines from the IL‐6 family and growth factors, such as EGF and PDGF. STAT3 activation and subsequent dimer formation initiates nuclear translocation of STAT3 for the regulation of target gene transcription. Four STAT3 isoforms have been identified, which have distinct biological functions. STAT3 is considered a proto‐oncogene and constitutive activation of STAT3 is implicated in the development of various cancers, including multiple myeloma, leukaemia and lymphomas. In this review, we focus on recent progress on STAT3 and osteosarcoma (OS). Notably, STAT3 is overexpressed and associated with the poor prognosis of OS. Constitutive activation of STAT3 in OS appears to upregulate the expression of target oncogenes, leading to OS cell transformation, proliferation, tumour formation, invasion, metastasis, immune evasion and drug resistance. Taken together, STAT3 is a target for cancer therapy, and STAT3 inhibitors represent potential therapeutic candidates for the treatment of OS. Signal transducer and activator of transcription 3 (STAT3) is a member of the STAT protein family, vitally important for eukaryotic cells. We review the molecular structure and function of STAT3 and its isoforms, highlighting signalling pathways for the regulation of gene transcription. A critical appraisal of STAT3 in cancers, such as osteosarcoma, is provided emphasizing potential therapeutic approaches targeting STAT3 and its inhibitors
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.5
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