Non-tumor tissue derived interleukin-17B activates IL-17RB/AKT/β-catenin pathway to enhance the stemness of gastric cancer.
Non-tumor tissue derived interleukin-17B activates IL-17RB/AKT/β-catenin pathway to enhance the stemness of gastric cancer.
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DOI：
10.1038/srep25447
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发表时间：
2016-05-05
影响因子：
4.6
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Bie Q;Sun C;Gong A;Li C;Su Z;Zheng D;Ji X;Wu Y;Guo Q;Wang S;Xu H
炎症是参与肿瘤进展的关键组成部分。白细胞介素-17（IL-17）属于与癌症进展相关的相对较新的细胞因子家族。但IL-17 B/IL-17 RB（IL-17受体B）信号通路在胃癌干细胞性中的作用尚不清楚。在此，我们证实了IL-17 RB在胃癌组织中的表达显著增加，过表达与胃癌患者的不良预后相关，并且过表达与一些干性标志物正相关。有趣的是，IL-17 B的表达在患者血清中而不是胃肿瘤组织中上调。此外，外源性rIL-17 B可显著促进依赖于IL-17 RB的胃癌细胞的干性，并诱导IL-17 RB的表达。同时，rIL-17 B处理后，MGC-803细胞磷酸化AKT、GSK-3β和β-catenin的表达以及β-catenin的核转位均呈剂量依赖性增加。AKT抑制剂LY 294002和AKT表达的敲低逆转了rIL-17 B诱导的β-连环蛋白和一些干性标志物的上调。综上所述，IL-17 B/IL-17 RB信号能够促进胃癌细胞的生长和迁移，并通过激活AKT/β-catenin通路上调细胞的干细胞性，提示IL-17 RB可能成为胃癌治疗的新靶点。
Inflammation is a critical component involved in tumor progression. Interleukin-17 (IL-17) belongs to a relatively new family of cytokines that has been associated with the progression of cancers. However, the role of IL-17B/IL-17RB (IL-17 receptor B) signaling to stemness of gastric cancer remains unknown. Here, we confirmed that the expression of IL-17RB in gastric cancer tissues was significantly increased, that overexpression was associated with poor prognosis of gastric cancer patients, and that overexpression was positively correlated with some stemness markers. Interestingly, the expression of IL-17B was upregulated in patient serum rather than gastric tumor tissues. Furthermore, exogenous rIL-17B significantly promoted the stemness of gastric cancer cells depending on IL-17RB and induced the expression of IL-17RB. Simultaneously, the expression of phosphorylated AKT, GSK-3β, and β-catenin as well as the nuclear translocation of β-catenin were significantly increased in the MGC-803 cell in a dose-dependent manner, when treated with rIL-17B. The AKT inhibitor, LY294002, and the knockdown of AKT expression reversed the rIL-17B-induced upregulation of β-catenin and some stemness markers. Together, our results indicate that the IL-17B/IL-17RB signal can promote the growth and migration of tumor cells, and upregulate cell stemness through activating the AKT/β-catenin pathway in gastric cancer, suggesting that IL-17RB may be a novel target in human gastric cancer therapy.