Loss of RACK1 Promotes Metastasis of Gastric Cancer by Inducing a miR-302c/IL8 Signaling Loop

被引：81

作者：

Chen, Ling ^{[1
]}

Min, Lingqiang ^{[1
]}

Wang, Xuefei ^{[1
]}

Zhao, Junjie ^{[1
]}

Chen, Hua ^{[2
]}

Qin, Jing ^{[1
]}

Chen, Weidong ^{[1
]}

Shen, Zhenbin ^{[1
]}

Tang, Zhaoqing ^{[1
]}

Gan, Qiangjun ^{[1
]}

Ruan, Yuanyuan ^{[3
]}

Sun, Yihong ^{[1
]}

Qin, Xinyu ^{[1
]}

Gu, Jianxin ^{[3
]}

机构：

[1] Fudan Univ, Dept Gen Surg, Zhongshan Hosp, Shanghai 200032, Peoples R China

[2] Oklahoma State Univ, Dept Stat, Stillwater, OK 74078 USA

[3] Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Shanghai 200433, Peoples R China

来源：

CANCER RESEARCH | 2015年 / 75卷 / 18期

关键词：

INTERLEUKIN-8; EXPRESSION; PROTEIN; TUMORIGENESIS; STATISTICS; CARCINOMA; INVASION; FEATURES; CELLS;

D O I：

10.1158/0008-5472.CAN-14-3690

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Gastric cancer remains the third leading cause of cance-rrelated mortality worldwide, and invasion and metastasis of gastric cancer represent the major reason for its poor prognosis. In this study, we found that loss of the receptor for activated C-kinase 1 (RACK1) promoted the metastasis of gastric cancer by enhancing the autocrine of IL8 in vitro and in vivo. microRNA (miRNA; miR) array identified that RACK1 modulated the expression of a series of miRNAs, including the miR-302 cluster, and RACK1 modulated the IL8 expression and tumor invasion through miRNA-302c. Moreover, upregulation of IL8 in turn decreased the level of miRNA-302c and induced IL8 expression in a feedback manner. Tissue microarray also indicated that RACK1 was correlated with invasion/metastasis phenotype, IL8 expression, as well as 5-year survival in clinical cases of gastric cancer. Together, our results imply that loss of RACK1 in gastric cancer links epigenetics to inflammatory cytokines to promote tumor metastasis. (C) 2015 AACR.

引用

页码：3832 / 3841

页数：10

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