文章：

在治疗上利用STAT3在癌症中的活性-使用组织修复作为路线图

Therapeutically exploiting STAT3 activity in cancer — using tissue repair as a road map

原文发布日期：2018-12-21

DOI: 10.1038/s41568-018-0090-8

类型: Review Article

开放获取: 否

英文摘要：

The tightly orchestrated temporal and spatial control of signal transducer and activator of transcription 3 (STAT3) activity in epithelial, immune and stromal cells is critical for wound healing and tissue repair. Excessive STAT3 activation within cancer cells and cells of the tumour microenvironment can be viewed as a neoplastic mimic of an inflammation-driven repair response that collectively promotes tumour progression. In addition to the canonical transcriptional pathways by which STAT3 promotes stem cell-like characteristics, survival, proliferation, metastatic potential and immune evasion, cytoplasmic STAT3 activity fuels tumour growth by metabolic and other non-transcriptional mechanisms. Here, we review the tumour-modulating activities of STAT3 in light of its role as a signalling node integrating inflammatory responses during wound healing. Accordingly, many of the cytokines that contribute to the para-inflammatory state of most solid malignancies converge on and underpin dysregulated STAT3 activity. Targeting of these cytokines, their cognate receptors and associated signalling cascades in clinical trials is beginning to demonstrate therapeutic efficacy, given that interference with STAT3 activity is likely to simultaneously curb the growth of cancer cells and augment antitumour immunity.

摘要翻译： 

信号转导及转录激活因子3（STAT3）在上皮细胞、免疫细胞和基质细胞中受到严格有序的时空调控，这一过程对伤口愈合和组织修复至关重要。癌细胞和肿瘤微环境中细胞的过度STAT3激活可被视为炎症驱动修复反应的肿瘤性模拟，共同促进肿瘤进展。除了STAT3通过经典转录途径促进干细胞样特性、存活、增殖、转移潜能和免疫逃逸外，细胞质中的STAT3活性还通过代谢和其他非转录机制推动肿瘤生长。本文结合STAT3在伤口愈合过程中整合炎症反应的信令节点作用，综述其肿瘤调控活性。相应地，大多数实体恶性肿瘤副炎症状态所涉及的多种细胞因子会汇聚并支撑STAT3的失调活性。鉴于干扰STAT3活性可能同时抑制癌细胞生长和增强抗肿瘤免疫力，针对这些细胞因子、其同源受体及相关信号通路的临床试验已开始展现治疗成效。

原文链接：

Therapeutically exploiting STAT3 activity in cancer — using tissue repair as a road map