Stat3: linking inflammation to epithelial cancer - more than a "gut" feeling?
Stat3: linking inflammation to epithelial cancer - more than a "gut" feeling?
复制标题
DOI：
10.1186/1747-1028-5-14
复制
发表时间：
2010-05-17
期刊：
影响因子：
2.3
通讯作者：
Ernst M
中科院分区：
文献类型：
--
作者：
Jarnicki A;Putoczki T;Ernst M
炎症是促进肿瘤发生和已建立的癌性病变进展的重要环境因素，最近的研究已经开始剖析连接这两种病理的机制。这些炎症和感染性疾病触发免疫和基质细胞释放可溶性介质，从而以旁分泌方式促进肿瘤细胞的生存和增殖。此外，影响癌基因、肿瘤抑制基因、染色体重排和扩增的（表型）基因突变触发肿瘤微环境内炎症介质的释放，以自分泌方式促进肿瘤生长。这两种途径在肿瘤细胞中会聚，并导致潜在信号转导子和转录激活子3（Stat 3）的激活，其介导有利于存活、增殖和血管生成的转录应答。在肿瘤微环境中激活Stat 3的细胞因子的丰度，其包括白细胞介素（IL）IL 6、IL 10和IL 17/23家族的成员，支持同时促进肿瘤上皮生长、刺激炎症和抑制宿主的抗肿瘤免疫应答的信号传导网络。因此，异常和持续的Stat 3激活是上皮来源的人类癌症中的常见观察结果，并且通常与不良结果相关。在这里，我们总结的见解从小鼠窝藏突变的Stat 3信号级联的组件，特别是gp 130，IL 6家族的细胞因子的共享受体。我们专注于各种反馈和前馈回路，其中Stat 3提供了肿瘤细胞及其微环境中的信号节点，从而在功能上将过度炎症与肿瘤生长联系起来。虽然这些观察结果与胃肠道肿瘤特别相关，但我们认为肿瘤对持续Stat 3激活的依赖可能也会影响其他上皮细胞来源的癌症。这些见解为gp 130/Stat 3信号级联在治疗靶向癌症中的明智干扰提供了线索。
Inflammation is an important environmental factor that promotes tumourigenesis and the progression of established cancerous lesions, and recent studies have started to dissect the mechanisms linking the two pathologies. These inflammatory and infectious conditions trigger immune and stromal cell release of soluble mediators which facilitate survival and proliferation of tumour cells in a paracrine manner. In addition, (epi-)genetic mutations affecting oncogenes, tumour-suppressor genes, chromosomal rearrangements and amplifications trigger the release of inflammatory mediators within the tumour microenvironment to promote neoplastic growth in an autocrine manner. These two pathways converge in tumour cells and result in activation of the latent signal transducer and activator of transcription 3 (Stat3) which mediates a transcriptional response favouring survival, proliferation and angiogenesis. The abundance of cytokines that activate Stat3 within the tumour microenvironment, which comprises of members of the interleukin (IL) IL6, IL10 and IL17/23 families, underpins a signaling network that simultaneously promotes the growth of neoplastic epithelium, fuels inflammation and suppresses the host's anti-tumour immune response. Accordingly, aberrant and persistent Stat3 activation is a frequent observation in human cancers of epithelial origin and is often associated with poor outcome. Here we summarize insights gained from mice harbouring mutations in components of the Stat3 signaling cascade and in particular of gp130, the shared receptor for the IL6 family of cytokines. We focus on the various feed-back and feed-forward loops in which Stat3 provides the signaling node in cells of the tumour and its microenvironment thereby functionally linking excessive inflammation to neoplastic growth. Although these observations are particularly pertinent to gastrointestinal tumours, we suggest that the tumour's addiction to persistent Stat3 activation is likely to also impact on other epithelial cell-derived cancers. These insights provide clues to the judicious interference of the gp130/Stat3 signaling cascade in therapeutically targeting cancer.
登录
查看更多内容
影响因子：
82.9
作者：
Chiarle, R;Simmons, WJ;Inghirami, G
通讯作者：
Inghirami, G
影响因子：
15.9
作者：
Bromberg, J
通讯作者：
Bromberg, J
DOI：
10.1073/pnas.0600666103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Chen, Zhi;Laurence, Arian;O'Shea, John J.
通讯作者：
O'Shea, John J.
影响因子：
4.5
作者：
Buchert M;Athineos D;Abud HE;Burke ZD;Faux MC;Samuel MS;Jarnicki AG;Winbanks CE;Newton IP;Meniel VS;Suzuki H;Stacker SA;Näthke IS;Tosh D;Huelsken J;Clarke AR;Heath JK;Sansom OJ;Ernst M
通讯作者：
Ernst M
影响因子：
10.5
作者：
Ancrile, Brooke;Lim, Kian-Huat;Counter, Christopher M.
通讯作者：
Counter, Christopher M.