Enhanced p62-NRF2 Feedback Loop due to Impaired Autophagic Flux Contributes to Arsenic-Induced Malignant Transformation of Human Keratinocytes
Joint Authors
Wang, Huihui
Zhao, Rui
Xu, Yuanyuan
Pi, Jingbo
Wu, Xiafang
Sun, Ru
Yang, Bei
Wang, Fang
Xu, Hongtao
Chen, Shimin
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-10-30
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Chronic exposure to arsenic induces a variety of cancers, particularly in the skin.
Autophagy is a highly conserved process which plays a dual role in tumorigenesis.
In the present study, we found that chronic exposure to an environmentally relevant dose of arsenite induced malignant transformation of human keratinocytes (HaCaT) with dysregulated autophagy as indicated by an increased number of autophagosomes, activation of mTORC1 pathway, and elevated protein levels of p62 and LC3II.
Meanwhile, arsenite-transformed cells showed lower intracellular levels of reactive oxygen species compared with control.
Silencing p62 ameliorated elevation in mRNA levels of NRF2 downstream genes (AKR1C1 and NQO1) and malignant phenotypes (acquired invasiveness and anchor-independent growth) induced by chronic arsenite exposure.
On the other hand, silencing NRF2 abrogated the increase in mRNA and protein levels of p62 and malignant phenotypes induced by arsenite.
In response to acute arsenite exposure, impaired autophagic flux with an increase in p62 protein level and interrupted autophagosome-lysosome fusion was observed.
The increase in p62 protein levels in response to arsenite was not completely dependent on NRF2 activation and at least partially attributed to protein degradation.
Our data indicate that accumulation of p62 by impaired autophagic flux is involved in the activation of NRF2 and contributes to skin tumorigenesis due to chronic arsenite exposure.
American Psychological Association (APA)
Wu, Xiafang& Sun, Ru& Wang, Huihui& Yang, Bei& Wang, Fang& Xu, Hongtao…[et al.]. 2019. Enhanced p62-NRF2 Feedback Loop due to Impaired Autophagic Flux Contributes to Arsenic-Induced Malignant Transformation of Human Keratinocytes. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1202000
Modern Language Association (MLA)
Wu, Xiafang…[et al.]. Enhanced p62-NRF2 Feedback Loop due to Impaired Autophagic Flux Contributes to Arsenic-Induced Malignant Transformation of Human Keratinocytes. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-12.
https://search.emarefa.net/detail/BIM-1202000
American Medical Association (AMA)
Wu, Xiafang& Sun, Ru& Wang, Huihui& Yang, Bei& Wang, Fang& Xu, Hongtao…[et al.]. Enhanced p62-NRF2 Feedback Loop due to Impaired Autophagic Flux Contributes to Arsenic-Induced Malignant Transformation of Human Keratinocytes. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1202000
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202000