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

Gastric cancer remains the third leading cause of cancer-related 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...

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Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 2015-09, Vol.75 (18), p.3832-3841
Hauptverfasser: Chen, Ling, Min, Lingqiang, Wang, Xuefei, Zhao, Junjie, Chen, Hua, Qin, Jing, Chen, Weidong, Shen, Zhenbin, Tang, Zhaoqing, Gan, Qiangjun, Ruan, Yuanyuan, Sun, Yihong, Qin, Xinyu, Gu, Jianxin
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Sprache:eng
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Zusammenfassung:Gastric cancer remains the third leading cause of cancer-related 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 expression 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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-14-3690