KRAS/NF-κB/YY1/miR-489 Signaling Axis Controls Pancreatic Cancer Metastasis

被引：85

作者：

Yuan, Peng ^{[1
,2
]}

He, Xiao-Hong ^{[1
,2
]}

Rong, Ye-Fei ^{[3
]}

Cao, Jing ^{[4
]}

Li, Yong ^{[5
]}

Hu, Yun-Ping ^{[6
]}

Liu, Yingbin ^{[6
]}

Li, Dangsheng ^{[7
]}

Lou, Wenhui ^{[3
]}

Liu, Mo-Fang ^{[1
,2
]}

机构：

[1] Univ Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol, Ctr RNA Res, Shanghai, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai Key Lab Mol Androl, Shanghai, Peoples R China

[3] Zhong Shan Hosp, Dept Pancreat Surg, 180 Fenglin Rd, Shanghai 200032, Peoples R China

[4] Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China

[5] Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44106 USA

[6] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Gen Surg, Shanghai, Peoples R China

[7] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Informat Ctr Life Sci, Shanghai, Peoples R China

来源：

CANCER RESEARCH | 2017年 / 77卷 / 01期

基金：

中国国家自然科学基金;

关键词：

NF-KAPPA-B; BREAST-CANCER; DUCTAL ADENOCARCINOMA; TRANSCRIPTION FACTOR; MICRORNA EXPRESSION; SKELETAL MYOGENESIS; CELL INVASION; INFLAMMATION; KRAS; YY1;

D O I：

10.1158/0008-5472.CAN-16-1898

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

KRAS activation occurring in more than 90% of pancreatic ductal adenocarcinomas (PDAC) drives progression and metastasis, but the underlying mechanisms involved in these processes are still poorly understood. Here, we show how KRAS acts through inflammatory NF-B-k signaling to activate the transcription factor YY1, which represses expression of the tumor suppressor gene miR-489. In PDAC cells, repression of miR-489 by KRAS signaling inhibited migration and metastasis by targeting the extracellular matrix factors ADAM9 and MMP7. miR-489 downregulation elevated levels of ADAM9 and MMP7, thereby enhancing the migration and metastasis of PDAC cells. Together, our results establish a pivotal mechanism of PDAC metastasis and suggest miR-489 as a candidate therapeutic target for their attack. (C) 2016 AACR.

引用

页码：100 / 111

页数：12

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