GCN5 inhibition prevents IL-6-induced prostate cancer metastases through PI3K/PTEN/Akt signaling by inactivating Egr-1

被引：24
作者：
Shao, Guangfeng [1 ]
Liu, Yuqiang [1 ]
Ma, Tianjia [1 ]
Zhang, Lei [1 ]
Yuan, Mingzhen [1 ]
Zhao, Shengtian [1 ,2 ,3 ,4 ]
机构：
[1] Shandong Univ, Hosp 2, Dept Urol, Jinan 250033, Shandong, Peoples R China
[2] Shandong Prov Hosp, Jinan 250021, Shandong, Peoples R China
[3] Key Lab Kindey Regenerat Shandong Prov, Jinan 250033, Shandong, Peoples R China
[4] Shandong Univ Karolinska Inst Collaborat Lab Stem, Jinan 250033, Shandong, Peoples R China
来源：
BIOSCIENCE REPORTS | 2018年 / 38卷
关键词：
LUNG-CANCER; EXPRESSION; INFLAMMATION; ACTIVATION; CELLS; IL-6; INTERLEUKIN-6; SURVIVAL; PATHWAY; E2F1;
D O I：
10.1042/BSR20180816
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
General control non-derepressible 5 (GCN5) is ectopically expressed in different types of human cancer and association with the carcinogenesis, development, and poor prognosis of cancers. The present study was aimed to investigate the potential role and related mechanisms of GCN5 in IL-6-treated prostate cancer (PCa) cell. The results showed that an elevated GCN5 expression was stimulated by IL-6. Knockdown of GCN5 significantly inhibited IL-6-driven proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Moreover, early growth response-1 (Egr-1) expression was elevated by IL-6 treatment and GCN5 siRNA down-regulated the expression of Egr-1. Furthermore, overexpression of Egr-1 attenuated the effects of GCN5 silence on cell proliferation, migration, invasion, and EMT in PCa. Besides, knockdown of GCN5 resulted in the down-regulation of p-Akt and up-regulation of PTEN, which was partly impeded by Egr-1 overexpression. The effects of GCN5 overexpression on cell proliferation and invasion were suppressed by LY294002, In conclusion, these data demonstrated the negative effect of up-regulated GCN5 in IL-6-induced metastasis and EMT in PCa cells through PI3K/PTEN/Akt signaling pathway down-regulating Egr-1 expression.
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页数：9
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