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

被引：84

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

共 50 条

[41] Ectopic Expression of miR-532-3p Suppresses Bone Metastasis of Prostate Cancer Cells via Inactivating NF-κB Signaling [J].

Wa, Qingde ;

Zou, Changye ;

Lin, Zhuoyuan ;

Huang, Sheng ;

Peng, Xinsheng ;

Yang, Chunxiao ;

Ren, Dong ;

Xu, Dongchu ;

Guo, Yuanqing ;

Liao, Zhuangwen ;

Wang, Bin ;

Hu, Hailan ;

Huang, Shuai ;

He, Peiheng .

MOLECULAR THERAPY-ONCOLYTICS, 2020, 17 :267-277

[42] Involvement of the NF-κB signaling pathway in proliferation and invasion inhibited by Zwint-1 deficiency in Pancreatic Cancer Cells [J].

Kim, Jae Hyeong ;

Youn, Yuna ;

Lee, Jong-chan ;

Kim, Jaihwan ;

Hwang, Jin-Hyeok .

JOURNAL OF CANCER, 2020, 11 (19) :5601-5611

[43] Cullin-5 Adaptor SPSB1 Controls NF-κB Activation Downstream of Multiple Signaling Pathways [J].

Georgana, Iliana ;

Maluquer de Motes, Carlos .

FRONTIERS IN IMMUNOLOGY, 2020, 10

[44] NEMO/NF-κB signaling functions as a double-edged sword in PanIN formation versus progression to pancreatic cancer [J].

Tsesmelis, Miltiadis ;

Buettner, Ulrike F. G. ;

Gerstenlauer, Melanie ;

Manfras, Uta ;

Tsesmelis, Konstantinos ;

Du, Ziwei ;

Sperb, Nadine ;

Weissinger, Stephanie Ellen ;

Moeller, Peter ;

Barth, Thomas F. E. ;

Maier, Harald J. ;

Chan, Lap Kwan ;

Wirth, Thomas .

MOLECULAR CANCER, 2024, 23 (01)

[45] ErbB receptor tyrosine kinase/NF-κB signaling controls mammosphere formation in human breast cancer [J].

Hinohara, Kunihiko ;

Kobayashi, Seiichiro ;

Kanauchi, Hajime ;

Shimizu, Seiichiro ;

Nishioka, Kotoe ;

Tsuji, Ei-ichi ;

Tada, Kei-ichiro ;

Umezawa, Kazuo ;

Mori, Masaki ;

Ogawa, Toshihisa ;

Inoue, Jun-ichiro ;

Tojo, Arinobu ;

Gotoh, Noriko .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (17) :6584-6589

[46] REGγ Controls Hippo Signaling and Reciprocal NF-κB-YAP Regulation to Promote Colon Cancer [J].

Wang, Qingwei ;

Gao, Xiao ;

Yu, Tong ;

Yuan, Lei ;

Dai, Jie ;

Wang, Weicang ;

Chen, Geng ;

Jiao, Chan ;

Zhou, Wang ;

Huang, Quan ;

Cui, Long ;

Zhang, Pei ;

Moses, Robb E. ;

Yang, Jianhua ;

Chen, Fengyuan ;

Fu, Junjiang ;

Xiao, Jianru ;

Li, Lei ;

Dang, Yongyan ;

Li, Xiaotao .

CLINICAL CANCER RESEARCH, 2018, 24 (08) :2015-2025

[47] Targeting NF-κB signaling pathway suppresses tumor growth, angiogenesis, and metastasis of human esophageal cancer [J].

Li, Bin ;

Li, Yuk Yin ;

Tsao, Sai Wah ;

Cheung, Annie L. M. .

MOLECULAR CANCER THERAPEUTICS, 2009, 8 (09) :2635-2644

[48] ADAMTS7 Enhances Gastric Cancer Growth and Metastasis by Triggering the NF-κB Signaling Pathway [J].

Chen, Shun ;

He, Jiancheng ;

Gao, Hanxu ;

Gao, Xian ;

Dai, Lingchen ;

Chen, Junjie ;

Sha, Zhenyu .

JOURNAL OF CANCER, 2025, 16 (03) :1008-1019

[49] ICAT promotes colorectal cancer metastasis via binding to JUP and activating the NF-κB signaling pathway [J].

Wang, Zihan ;

Hu, Jiancong ;

Chen, Junxiong ;

Zhang, Jingdan ;

Li, Weiqian ;

Tian, Yu ;

Liu, Huanliang ;

Yang, Xiangling .

JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2022, 36 (10)

[50] Targeting AGTR1/NF-κB/CXCR4 axis by miR-155 attenuates oncogenesis in glioblastoma [J].

Singh, Anukriti ;

Srivastava, Nidhi ;

Yadav, Anjali ;

Ateeq, Bushra .

NEOPLASIA, 2020, 22 (10) :497-510

← 1 2 3 4 5 →