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The SGK3-Catalase antioxidant signaling axis drives cervical cancer growth and therapy resistance
Cancer cells frequently exhibit aberrant redox homeostasis and adaptation to oxidative stress. Hence abrogation of redox adaptation in cancer cells can be exploited for therapeutic benefit. Here we report SGK3 functions as an anti-oxidative factor to promote cell growth and drug resistance in cervic...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623367/ https://www.ncbi.nlm.nih.gov/pubmed/37866161 http://dx.doi.org/10.1016/j.redox.2023.102931 |
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author | Wang, Min Liu, Jiannan Liao, Xingming Yi, Yasong Xue, Yijue Yang, Ling Cheng, Hailing Liu, Pixu |
author_facet | Wang, Min Liu, Jiannan Liao, Xingming Yi, Yasong Xue, Yijue Yang, Ling Cheng, Hailing Liu, Pixu |
author_sort | Wang, Min |
collection | PubMed |
description | Cancer cells frequently exhibit aberrant redox homeostasis and adaptation to oxidative stress. Hence abrogation of redox adaptation in cancer cells can be exploited for therapeutic benefit. Here we report SGK3 functions as an anti-oxidative factor to promote cell growth and drug resistance in cervical cancers harboring PIK3CA helical domain mutations. Mechanistically, SGK3 is activated upon oxidative stress and exerts anti-ROS activity by stabilizing and activating the antioxidant enzyme catalase. SGK3 interacts with and phosphorylates catalase, promoting its tetrameric state and activity. Meanwhile, SGK3 phosphorylates GSK3β and protects catalase from GSK3β-β-TrCP mediated ubiquitination and proteasomal degradation. Furthermore, SGK3 inhibition not only potentiates CDK4/6 inhibitor Palbociclib-mediated cytotoxicity, but also overcomes cisplatin resistance through ROS-mediated mechanisms. These data uncover the role of SGK3 in maintaining redox homeostasis and suggest that the SGK3-catalase antioxidant signaling axis may be therapeutically targeted to improve treatment efficacy for cervical cancers carrying PIK3CA helical domain mutations. |
format | Online Article Text |
id | pubmed-10623367 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-106233672023-11-04 The SGK3-Catalase antioxidant signaling axis drives cervical cancer growth and therapy resistance Wang, Min Liu, Jiannan Liao, Xingming Yi, Yasong Xue, Yijue Yang, Ling Cheng, Hailing Liu, Pixu Redox Biol Research Paper Cancer cells frequently exhibit aberrant redox homeostasis and adaptation to oxidative stress. Hence abrogation of redox adaptation in cancer cells can be exploited for therapeutic benefit. Here we report SGK3 functions as an anti-oxidative factor to promote cell growth and drug resistance in cervical cancers harboring PIK3CA helical domain mutations. Mechanistically, SGK3 is activated upon oxidative stress and exerts anti-ROS activity by stabilizing and activating the antioxidant enzyme catalase. SGK3 interacts with and phosphorylates catalase, promoting its tetrameric state and activity. Meanwhile, SGK3 phosphorylates GSK3β and protects catalase from GSK3β-β-TrCP mediated ubiquitination and proteasomal degradation. Furthermore, SGK3 inhibition not only potentiates CDK4/6 inhibitor Palbociclib-mediated cytotoxicity, but also overcomes cisplatin resistance through ROS-mediated mechanisms. These data uncover the role of SGK3 in maintaining redox homeostasis and suggest that the SGK3-catalase antioxidant signaling axis may be therapeutically targeted to improve treatment efficacy for cervical cancers carrying PIK3CA helical domain mutations. Elsevier 2023-10-16 /pmc/articles/PMC10623367/ /pubmed/37866161 http://dx.doi.org/10.1016/j.redox.2023.102931 Text en © 2023 The Authors. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Wang, Min Liu, Jiannan Liao, Xingming Yi, Yasong Xue, Yijue Yang, Ling Cheng, Hailing Liu, Pixu The SGK3-Catalase antioxidant signaling axis drives cervical cancer growth and therapy resistance |
title | The SGK3-Catalase antioxidant signaling axis drives cervical cancer growth and therapy resistance |
title_full | The SGK3-Catalase antioxidant signaling axis drives cervical cancer growth and therapy resistance |
title_fullStr | The SGK3-Catalase antioxidant signaling axis drives cervical cancer growth and therapy resistance |
title_full_unstemmed | The SGK3-Catalase antioxidant signaling axis drives cervical cancer growth and therapy resistance |
title_short | The SGK3-Catalase antioxidant signaling axis drives cervical cancer growth and therapy resistance |
title_sort | sgk3-catalase antioxidant signaling axis drives cervical cancer growth and therapy resistance |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623367/ https://www.ncbi.nlm.nih.gov/pubmed/37866161 http://dx.doi.org/10.1016/j.redox.2023.102931 |
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