KRAS/NF-κB/YY1/miR-489 Signaling Axis Controls Pancreatic Cancer Metastasis
Authors: Mo-Fang Liu
Jing Cao
Yong Li
Peng Yuan
Yingbin Liu
Dangsheng Li
Wenhui Lou
Ye-Fei Rong
Xiao-Hong He
Yun-Ping Hu
Journal: Cancer research (2017)
Discipline: CLINICAL MEDICINE
Keywords: KRAS activation; pancreatic ductal adenocarcinomas; progression; metastasis; NF-κB signaling
Affiliations: 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., Department of Pancreatic Surgery, Zhong Shan Hospital, Shanghai, China., School of Life Science and Technology, Shanghai Tech University, Shanghai, China., Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio., Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China., Shanghai Information Center for Life Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China., Department of Pancreatic Surgery, Zhong Shan Hospital, Shanghai, China.  ., 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.  .

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. 

Retracted: No

PubPeer comments:
 Figures 1 and 5. Some panels in Figures 1D, 1H, and 5B appear to be visible multiple times or show an overlap. Boxes of the same color show areas that look similar. Brought to my attention by a reader. ![file] , 
 Dear Dr. Bik, I got you message. Thank you very much for your comments on our paper. I will take a look at our original data regarding the figure panels and respond to you as soon as possible. Many thanks again. Best regards Mofang , 
 Dear Dr. Bik, Due to the figure files too big to be uploaded, I replied your email with figure files attached. Wish you will be able to receive my email. Thanks! Mofang , 
 #3 Dear Dr. Bik, Thank you again for your comment on our paper. After receiving your comments, we have carefully checked the indicated trans-well images in Figures 1D, 1H and 5B and confirmed errors in these figure panels. Fortunately, we have had all the original images for the trans-well experiments that belong to these Figure panels saved in our computers. We found that the mistakes likely resulted from the incorporation of wrong figure panels due to high similarity in both file names and images from repeated data in the original data folder. We have been working with the journal to issue an erratum to fix the problem. Due to COVID-19 epidemic, the process is a little slowly. We will update you the information later. Many thanks again. Mofang , 
 2020 correction. https: cancerres.aacrjournals.org content 80 18 4022 In the original version of this article (1), there are errors in Figs. 1D and H and 5B. Specifically, in Fig. 1D, the same migration assay image was used in the second and seventh panels, and an overlapping image was used in the third and fourth panels. In addition, the same migration assay image was used in the fifth panel of Fig. 1D and in the fifth panel of Fig. 1H. Finally, an overlapping image was used in the second and third panels of Fig. 5B. The errors have been corrected in the latest online HTML and PDF versions of the article. The authors regret these errors. Reference 1.u21b5Yuan P, He XH, Rong YF, Cao J, Li Y, Hu YP, et al. KRAS NF-u03baB YY1 miR-489 signaling axis controls pancreatic cancer metastasis. Cancer Res 2017;77:100u201311. ,