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. 2018 Jun 7;8:210. doi: 10.3389/fonc.2018.00210

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Copyright © 2018 Ichimura and Komatsu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Tumorigenesis of cancer cells harboring phospho-p62. Accumulated p62 and ubiquitinated substrates form cytoplasmic protein aggregates in pre-malignant tumor cells (1). p62 is phosphorylated (2), and subsequently nuclear factor erythroid 2-related factor 2 (Nrf2) is activated (3). Mouse double minute 2 homolog (MDM2) induced by Nrf2 results in the increase of Notch signaling (4) and the reduction of p53, followed by cell malignancy (5). Abbreviations: PanIN, premalignant pancreatic intraepithelial neoplasia; PDAC, pancreatic ductal adenocarcinoma.