IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer.
IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer.
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DOI：
10.1016/j.ccr.2009.01.001
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发表时间：
2009-02-03
期刊：
影响因子：
50.3
通讯作者：
Karin M
中科院分区：
文献类型：
--
作者：
Grivennikov S;Karin E;Terzic J;Mucida D;Yu GY;Vallabhapurapu S;Scheller J;Rose-John S;Cheroutre H;Eckmann L;Karin M
结肠炎相关癌（CAC）是炎症性肠病最严重的并发症。促炎细胞因子被认为在CAC肿瘤发生过程中调节肿瘤前生长。白细胞介素6 （IL-6）是NF-κ b调控的多功能细胞因子，作用于上皮细胞和免疫细胞。利用遗传工具，我们现在证明IL-6在早期CAC肿瘤发生过程中是一个关键的肿瘤启动子。除了促进肿瘤起始细胞的增殖外，IL-6由固有层髓样细胞产生，保护正常和恶性前肠上皮细胞（IEC）免于凋亡。IL-6的增殖和生存作用主要由转录因子STAT3介导，其iec特异性消融对CAC肿瘤发生有深远影响。因此，NF-κB-IL-6-STAT3级联是肿瘤启动IEC增殖和存活的重要调节因子。
Colitis associated cancer (CAC) is the most serious complication of inflammatory bowel disease. Pro-inflammatory cytokines were suggested to regulate pre-neoplastic growth during CAC tumorigenesis. Interleukin 6 (IL-6) is a multifunctional NF-κB–regulated cytokine which acts on epithelial and immune cells. Using genetic tools we now demonstrate that IL-6 is a critical tumor promoter during early CAC tumorigenesis. In addition to enhancing proliferation of tumor initiating cells, IL-6 produced by lamina propria myeloid cells protects normal and pre-malignant intestinal epithelial cells (IEC) from apoptosis. The proliferative and survival effects of IL-6 are largely mediated by transcription factor STAT3, whose IEC-specific ablation has profound impact on CAC tumorigenesis. Thus, the NF-κB-IL-6-STAT3 cascade is an important regulator of the proliferation and survival of tumor initiating IEC.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
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作者：
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