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p62 promotes bladder cancer cell growth by activating KEAP1/NRF2‐dependent antioxidative response

p62 is associated with 2 major cellular defense mechanisms against metabolic and oxidative stress, autophagy and the Kelch‐like ECH‐associated protein 1 (KEAP1)‐nuclear factor‐E2‐related factor 2 (NRF2) system. Recent studies indicate that the p62‐KEAP1‐NRF2 pathway promotes tumorigenesis and tumor...

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Detalles Bibliográficos
Autores principales: Li, Tao, Jiang, Dali, Wu, Kaijie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156869/
https://www.ncbi.nlm.nih.gov/pubmed/31967368
http://dx.doi.org/10.1111/cas.14321
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author Li, Tao
Jiang, Dali
Wu, Kaijie
author_facet Li, Tao
Jiang, Dali
Wu, Kaijie
author_sort Li, Tao
collection PubMed
description p62 is associated with 2 major cellular defense mechanisms against metabolic and oxidative stress, autophagy and the Kelch‐like ECH‐associated protein 1 (KEAP1)‐nuclear factor‐E2‐related factor 2 (NRF2) system. Recent studies indicate that the p62‐KEAP1‐NRF2 pathway promotes tumorigenesis and tumor growth mediated by NRF2‐dependent antioxidative response. However, whether p62 is involved in bladder cancer (BCa) development remains unknown. Here, we found that p62 is overexpressed in BCa tissue and several BCa cell lines. The knockdown of p62 inhibits BCa cell growth both in vitro and in vivo, with increased intracellular reactive oxygen species level. Mechanically, p62 activates NRF2 signaling by sequestrating KEAP1, which leads to the upregulation of antioxidant genes (Gclc, Gstm5, and Gpx2), thus protecting BCa cells from oxidative stress. Our findings indicate that p62 might be involved in the development of BCa and serve as a potential therapeutic target.
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spelling pubmed-71568692020-04-20 p62 promotes bladder cancer cell growth by activating KEAP1/NRF2‐dependent antioxidative response Li, Tao Jiang, Dali Wu, Kaijie Cancer Sci Original Articles p62 is associated with 2 major cellular defense mechanisms against metabolic and oxidative stress, autophagy and the Kelch‐like ECH‐associated protein 1 (KEAP1)‐nuclear factor‐E2‐related factor 2 (NRF2) system. Recent studies indicate that the p62‐KEAP1‐NRF2 pathway promotes tumorigenesis and tumor growth mediated by NRF2‐dependent antioxidative response. However, whether p62 is involved in bladder cancer (BCa) development remains unknown. Here, we found that p62 is overexpressed in BCa tissue and several BCa cell lines. The knockdown of p62 inhibits BCa cell growth both in vitro and in vivo, with increased intracellular reactive oxygen species level. Mechanically, p62 activates NRF2 signaling by sequestrating KEAP1, which leads to the upregulation of antioxidant genes (Gclc, Gstm5, and Gpx2), thus protecting BCa cells from oxidative stress. Our findings indicate that p62 might be involved in the development of BCa and serve as a potential therapeutic target. John Wiley and Sons Inc. 2020-02-12 2020-04 /pmc/articles/PMC7156869/ /pubmed/31967368 http://dx.doi.org/10.1111/cas.14321 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Li, Tao
Jiang, Dali
Wu, Kaijie
p62 promotes bladder cancer cell growth by activating KEAP1/NRF2‐dependent antioxidative response
title p62 promotes bladder cancer cell growth by activating KEAP1/NRF2‐dependent antioxidative response
title_full p62 promotes bladder cancer cell growth by activating KEAP1/NRF2‐dependent antioxidative response
title_fullStr p62 promotes bladder cancer cell growth by activating KEAP1/NRF2‐dependent antioxidative response
title_full_unstemmed p62 promotes bladder cancer cell growth by activating KEAP1/NRF2‐dependent antioxidative response
title_short p62 promotes bladder cancer cell growth by activating KEAP1/NRF2‐dependent antioxidative response
title_sort p62 promotes bladder cancer cell growth by activating keap1/nrf2‐dependent antioxidative response
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156869/
https://www.ncbi.nlm.nih.gov/pubmed/31967368
http://dx.doi.org/10.1111/cas.14321
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