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. 2017 Feb 15;8:14228. doi: 10.1038/ncomms14228

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Copyright © 2017, The Author(s)

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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(a) The 334 surgical specimens of breast cancer were immunostained using antibodies against Dub3, Snail1, and the control serum (data not shown). Images with consecutive IHC staining of both Dub3 and Snail1 in six cases of breast tumours (top panel: three cases of negative staining; bottom panel: three cases of positive) are shown (Scale bars, 50 μm). Statistical analysis is shown Tables 1, 2, 3. (b) Kaplan–Meier plots of distant metastasis-free survival of patients, stratified by expression of Dub3. Data obtained from the TCGA and Finak database. P-values represent log-rank testing of the difference in cumulative survival. (c) A proposed model to illustrate Dub3 induces Snail1 stabilization through a deubiquitination event. IL-6 induces the expression of Dub3, which antagonizes the function Snail1's ubiquitin E3 ligase (such as FBXL14 and β-TRCP1), leading to Snail1 stabilization and the acquisition of EMT and metastasis.