title: KRAS/NF-κB/YY1/miR-489 Signaling Axis Controls Pancreatic Cancer Metastasis.
abstract: 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-κB 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. Cancer Res; 77(1); 100-11. ©2016 AACR.
authors: Center for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, CAS Center for Excellence in Molecular Cell Science, Shanghai, China.|Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Peng
authors: P
authors: Yuan
authors: Center for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, CAS Center for Excellence in Molecular Cell Science, Shanghai, China.|Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Xiao-Hong
authors: XH
authors: He
authors: Department of Pancreatic Surgery, Zhong Shan Hospital, Shanghai, China.
authors: Ye-Fei
authors: YF
authors: Rong
authors: School of Life Science and Technology, Shanghai Tech University, Shanghai, China.
authors: Jing
authors: J
authors: Cao
authors: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Yong
authors: Y
authors: Li
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Yun-Ping
authors: YP
authors: Hu
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Yingbin
authors: Y
authors: Liu
authors: Shanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Dangsheng
authors: D
authors: Li
authors: Department of Pancreatic Surgery, Zhong Shan Hospital, Shanghai, China. mfliu@sibcb.ac.cn lou.wenhui@zs-hospital.sh.cn.
authors: Wenhui
authors: W
authors: Lou
authors: Center for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, CAS Center for Excellence in Molecular Cell Science, Shanghai, China. mfliu@sibcb.ac.cn lou.wenhui@zs-hospital.sh.cn.|Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|School of Life Science and Technology, Shanghai Tech University, Shanghai, China.
authors: Mo-Fang
authors: MF
authors: Liu
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D064593:Heterografts; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D059467:Transcriptome; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; C552418:MIRN489 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D016283:Proto-Oncogene Proteins p21(ras)