Sphingosine-1-phosphate: Driver of NFκB and STAT3 persistent activation in chronic intestinal inflammation and colitis-associated cancer.
Sphingosine-1-phosphate: Driver of NFκB and STAT3 persistent activation in chronic intestinal inflammation and colitis-associated cancer.
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DOI：
10.4161/jkst.24150
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发表时间：
2013-07-01
期刊：
影响因子：
--
通讯作者：
Theiss AL
中科院分区：
文献类型：
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作者：
Theiss AL
炎症性肠病与结直肠癌的风险增加有关。结肠炎相关癌症是一种典型的炎症驱动的癌症，其中组成性NFκB和STAT3激活驱动肿瘤发生。Liang等人最近发表在《Cancer Cell》杂志上的研究表明，鞘氨醇激酶1 （SphK1）介导的鞘氨醇-1-磷酸（S1P）的上调驱动了一个持续的NFκB/IL-6/STAT3/鞘氨醇-1-磷酸受体1 （S1PR1）扩增环，这对慢性结肠炎和结肠炎相关癌症的发展至关重要。FTY720是一种S1PR1拮抗剂，可抑制持续的nf - κ b /IL-6/STAT3信号通路，减少结肠炎相关癌症的发生和进展。靶向SphK1/S1P/S1PR1可能为防止结肠炎发展为癌症提供了一种治疗选择。
Inflammatory bowel disease is associated with an increased risk of colorectal cancer. Colitis-associated cancer is a classical inflammation-driven cancer in which constitutive NFκB and STAT3 activation drive tumorigenesis. Recent findings published by Liang et al. in Cancer Cell demonstrate that sphingosine kinase 1 (SphK1)-mediated upregulation of sphingosine-1-phosphate (S1P) drives a persistent NFκB/IL-6/STAT3/sphingosine-1-phosphate receptor 1 (S1PR1) amplification loop that is critical to the development of chronic colitis and colitis-associated cancer. FTY720, an antagonist of S1PR1, abolished persistent NFκB/IL-6/STAT3 signaling and reduced the development and progression of colitis-associated cancer. Targeting SphK1/S1P/S1PR1 may provide a therapeutic option to prevent the progression of colitis to cancer.