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Title: Impaired autophagic flux and p62-mediated EMT are involved in arsenite-induced transformation of L-02 cells

Abstract

Autophagy is a catabolic process essential for preserving cellular homeostasis, and the epithelial-to-mesenchymal transition (EMT) is involved during tissue development and cancer progression. In arsenite-treated human hepatic epithelial (L-02) cells, arsenite reduced the autophagic flux, which caused accumulation of p62, an adaptor and receptor of autophagy. Further, in arsenite-transformed L-02 cells, the levels of E-cadherin were attenuated, but the levels of vimentin, which is expressed in mesenchymal cells, and Snail, a transcription regulator of the EMT, were up-regulated. Thus, after chronic exposure of L-02 cells to arsenite, the impaired autophagic flux induced the accumulation of p62, which up-regulated the expression of Snail, a protein involved in arsenite-induced EMT of these cells. Knockdown of p62 by siRNA reversed the arsenite-induced EMT and decreased the capacities of arsenite-transformed L-02 cells for colony formation and invasion and migration. Therefore, in arsenite-induced transformation of L-02 cells, the accumulation of p62, by impairing autophagic flux, mediates the EMT via Snail. These results provide a previously unknown mechanism underlying arsenic toxicity and carcinogenicity. - Highlights: • Impaired autophagic flux induces the accumulation of p62 in arsenite-treated L-02 cells. • The EMT is associated with arsenite-induced transformation in L-02 cells. • p62 mediates the EMT via Snailmore » in arsenite-induced transformation of L-02 cells.« less

Authors:
 [1];  [2];  [3]; ;  [1];  [2];  [4]; ;  [5]; ; ; ;  [1];  [2];  [4];  [3];  [5];
  1. Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu (China)
  2. (China)
  3. Jiangsu Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, People's Republic China (China)
  4. School of Public Health, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 510182, Guangdong, People's Republic China (China)
  5. The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 550025, Guizhou (China)
Publication Date:
OSTI Identifier:
22722946
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 334; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CHRONIC EXPOSURE; COLONY FORMATION; SNAILS; TRANSFORMATIONS

Citation Formats

Liu, Xinlu, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, Ling, Min, Chen, Chao, Luo, Fei, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, Yang, Ping, Wang, Dapeng, Chen, Xiong, Xu, Hui, Xue, Junchao, Yang, Qianlei, Lu, Lu, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, Lu, Jiachun, Bian, Qian, Zhang, Aihua, and others, and. Impaired autophagic flux and p62-mediated EMT are involved in arsenite-induced transformation of L-02 cells. United States: N. p., 2017. Web. doi:10.1016/J.TAAP.2017.09.004.
Liu, Xinlu, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, Ling, Min, Chen, Chao, Luo, Fei, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, Yang, Ping, Wang, Dapeng, Chen, Xiong, Xu, Hui, Xue, Junchao, Yang, Qianlei, Lu, Lu, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, Lu, Jiachun, Bian, Qian, Zhang, Aihua, & others, and. Impaired autophagic flux and p62-mediated EMT are involved in arsenite-induced transformation of L-02 cells. United States. doi:10.1016/J.TAAP.2017.09.004.
Liu, Xinlu, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, Ling, Min, Chen, Chao, Luo, Fei, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, Yang, Ping, Wang, Dapeng, Chen, Xiong, Xu, Hui, Xue, Junchao, Yang, Qianlei, Lu, Lu, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, Lu, Jiachun, Bian, Qian, Zhang, Aihua, and others, and. Wed . "Impaired autophagic flux and p62-mediated EMT are involved in arsenite-induced transformation of L-02 cells". United States. doi:10.1016/J.TAAP.2017.09.004.
@article{osti_22722946,
title = {Impaired autophagic flux and p62-mediated EMT are involved in arsenite-induced transformation of L-02 cells},
author = {Liu, Xinlu and The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu and Ling, Min and Chen, Chao and Luo, Fei and The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu and Yang, Ping and Wang, Dapeng and Chen, Xiong and Xu, Hui and Xue, Junchao and Yang, Qianlei and Lu, Lu and The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu and Lu, Jiachun and Bian, Qian and Zhang, Aihua and others, and},
abstractNote = {Autophagy is a catabolic process essential for preserving cellular homeostasis, and the epithelial-to-mesenchymal transition (EMT) is involved during tissue development and cancer progression. In arsenite-treated human hepatic epithelial (L-02) cells, arsenite reduced the autophagic flux, which caused accumulation of p62, an adaptor and receptor of autophagy. Further, in arsenite-transformed L-02 cells, the levels of E-cadherin were attenuated, but the levels of vimentin, which is expressed in mesenchymal cells, and Snail, a transcription regulator of the EMT, were up-regulated. Thus, after chronic exposure of L-02 cells to arsenite, the impaired autophagic flux induced the accumulation of p62, which up-regulated the expression of Snail, a protein involved in arsenite-induced EMT of these cells. Knockdown of p62 by siRNA reversed the arsenite-induced EMT and decreased the capacities of arsenite-transformed L-02 cells for colony formation and invasion and migration. Therefore, in arsenite-induced transformation of L-02 cells, the accumulation of p62, by impairing autophagic flux, mediates the EMT via Snail. These results provide a previously unknown mechanism underlying arsenic toxicity and carcinogenicity. - Highlights: • Impaired autophagic flux induces the accumulation of p62 in arsenite-treated L-02 cells. • The EMT is associated with arsenite-induced transformation in L-02 cells. • p62 mediates the EMT via Snail in arsenite-induced transformation of L-02 cells.},
doi = {10.1016/J.TAAP.2017.09.004},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 334,
place = {United States},
year = {2017},
month = {11}
}