As an independent unfavorable prognostic factor, IL-8 promotes metastasis of nasopharyngeal carcinoma through induction of epithelial-mesenchymal transition and activation of AKT signaling.
As an independent unfavorable prognostic factor, IL-8 promotes metastasis of nasopharyngeal carcinoma through induction of epithelial-mesenchymal transition and activation of AKT signaling.
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DOI：
10.1093/carcin/bgs181
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发表时间：
2012-07
期刊：
影响因子：
4.7
通讯作者：
Qian CN
中科院分区：
文献类型：
--
作者：
Li XJ;Peng LX;Shao JY;Lu WH;Zhang JX;Chen S;Chen ZY;Xiang YQ;Bao YN;Zheng FJ;Zeng MS;Kang TB;Zeng YX;Teh BT;Qian CN
鼻咽癌是头颈部肿瘤中转移潜能最高的肿瘤。远处转移是治疗失败的主要原因。白细胞介素-8（IL-8）在鼻咽癌进展中的作用尚不清楚。我们对255例NPC患者的多变量生存分析显示，原发性NPC组织中IL-8的高表达是患者总生存期、无病生存期和无远处转移生存期的独立预后因素。体外实验结果显示，IL-8在已建立的高转移鼻咽癌细胞系S18中的表达高于低转移细胞系。通过短发夹RNA抑制IL-8降低了IL-8在S18细胞中的表达，随后抑制了细胞的迁移、侵袭和肝转移，而不影响细胞生长。IL-8在S26细胞中的过表达导致细胞的迁移、侵袭和转移能力增加而不影响细胞生长。外源性IL-8以剂量依赖方式促进低转移CNE-2细胞的迁移和侵袭。IL-8可诱导多种鼻咽癌细胞系发生上皮-间质转化（EMT）。通过敲低IL-8的表达，可以抑制S18细胞中高水平的磷酸化AKT。此外，IL-8促进的迁移和侵袭可以通过应用磷酸肌醇-3-激酶抑制剂LY 294002或通过使用小干扰RNA敲低AKT表达来消除。总之，IL-8可作为NPC患者总生存期、无病生存期和无转移生存期的独立预后指标。IL-8通过自分泌和旁分泌途径促进NPC细胞的转移，包括激活AKT信号通路，诱导NPC细胞发生EMT。
Nasopharyngeal carcinoma (NPC) has the highest metastatic potential among head and neck cancers. Distant metastasis is the major cause of treatment failure. The role of interleukin-8 (IL-8) in NPC progression remains unknown. Our multivariate survival analyses of 255 patients with NPC revealed that higher IL-8 expression in primary NPC tissue was an independent prognostic factor for overall survival, disease-free survival, and distant metastasis-free survival of the patients. In vitro study revealed that IL-8 was highly expressed in the established high-metastasis NPC clone S18 relative to the low-metastasis cells. Suppression of IL-8 by short-hairpin RNA reduced the expression of IL-8 in S18 cells and subsequently inhibited migration, invasion, and hepatic metastasis of the cells without influencing cellular growth. Overexpression of IL-8 in S26 cells resulted in increased migration, invasion, and metastasis capabilities of the cells without affecting cellular growth. Exogenous IL-8 enhanced the migration and invasion of low-metastasis CNE-2 cells in a dose-dependent manner. An epithelial–mesenchymal transition (EMT) could be induced by IL-8 in various NPC cell lines. The high level of phosphorylated AKT in S18 cells could be suppressed by knocking down IL-8 expression. Further, IL-8-promoted migration and invasion could be abolished by either the application of the phosphoinositide-3-kinase inhibitor LY294002 or the knock down of AKT expression by using small-interfering RNA. In summary, IL-8 serves as an independent prognostic indicator of overall survival, disease-free survival, and metastasis-free survival for patients with NPC. IL-8 promotes NPC metastasis via autocrine and paracrine means, involving activation of AKT signaling and inducing EMT in NPC cells.
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影响因子：
2.5
作者：
Liao, Bing;Zhong, Bi-Ling;Li, Bin
通讯作者：
Li, Bin
影响因子：
10.3
作者：
Pine, Sharon R.;Mechanic, Leah E.;Harris, Curtis C.
通讯作者：
Harris, Curtis C.
影响因子：
5.4
作者：
Hsu, Meichi;Wu, Shih-Yi;Chang, Yao
通讯作者：
Chang, Yao
DOI：
10.1084/jem.167.6.1883
发表时间：
1988-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Matsushima K;Morishita K;Yoshimura T;Lavu S;Kobayashi Y;Lew W;Appella E;Kung HF;Leonard EJ;Oppenheim JJ
通讯作者：
Oppenheim JJ
丝甘氨酸是鼻咽癌促进转移的治疗诊断靶点
影响因子：
11.2
作者：
Li, Xin-Jian;Ong, Choon Kiat;Qian, Chao-Nan
通讯作者：
Qian, Chao-Nan