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

Abstract

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.

• Authors: Ling Chen, Lingqiang Min, Xuefei Wang, Junjie Zhao, Hua Chen, Jing Qin, Weidong Chen, Zhenbin Shen, Zhaoqing Tang, Qiangjun Gan, Yuanyuan Ruan, Yihong Sun, Xinyu Qin, Jianxin Gu
• Journal: Cancer research (Cancer Res) Vol. 75 Issue 18 Pg. 3832-41 (Sep 15 2015) ISSN: 1538-7445 [Electronic] United States
• PMID: 26199092 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Interleukin-8
• MIRN302 microRNA, mouse
• MicroRNAs
• Neoplasm Proteins
• RACK1 protein, human
• RNA, Small Interfering
• Receptors for Activated C Kinase
• Receptors, Cell Surface
• Receptors, Interleukin-8
• GTP-Binding Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Autocrine Communication
• Female
• GTP-Binding Proteins (deficiency, genetics, physiology)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Interleukin-8 (biosynthesis, genetics, physiology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics)
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Metastasis (genetics)
• Neoplasm Proteins (deficiency, genetics, physiology)
• Peritoneal Neoplasms (secondary)
• RNA, Small Interfering (pharmacology)
• Receptors for Activated C Kinase
• Receptors, Cell Surface (deficiency, genetics, physiology)
• Receptors, Interleukin-8 (biosynthesis, genetics)
• Signal Transduction
• Stomach Neoplasms (genetics, mortality, pathology)