Energy-Stress-Mediated AMPK Activation Promotes GPX4-Dependent Ferroptosis through the JAK2/STAT3/P53 Axis in Renal Cancer

Energy stress is an unfavorable condition that tumor cells are often exposed to. Ferroptosis is considered an emerging target for tumor therapy. However, the role of ferroptosis in energy stress in renal cancer is currently unknown. In this study, we found that glucose deprivation significantly enha...

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Autores principales: Li, Yanze, Zhang, Ye, Qiu, Qiangmin, Wang, Lei, Mao, Hu, Hu, Juncheng, Chen, Zhiyuan, Du, Yang, Liu, Xiuheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554664/
https://www.ncbi.nlm.nih.gov/pubmed/36246395
http://dx.doi.org/10.1155/2022/2353115
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author Li, Yanze
Zhang, Ye
Qiu, Qiangmin
Wang, Lei
Mao, Hu
Hu, Juncheng
Chen, Zhiyuan
Du, Yang
Liu, Xiuheng
author_facet Li, Yanze
Zhang, Ye
Qiu, Qiangmin
Wang, Lei
Mao, Hu
Hu, Juncheng
Chen, Zhiyuan
Du, Yang
Liu, Xiuheng
author_sort Li, Yanze
collection PubMed
description Energy stress is an unfavorable condition that tumor cells are often exposed to. Ferroptosis is considered an emerging target for tumor therapy. However, the role of ferroptosis in energy stress in renal cancer is currently unknown. In this study, we found that glucose deprivation significantly enhanced GPX4-dependent ferroptosis through AMPK activation. Further, AMPK activation suppressed GPX4 expression at the transcriptional level through the upregulation of P53 expression. Additionally, the inactivation of JAK2/STAT3 transcriptionally promoted P53 expression, thereby promoting AMPK-mediated GPX4-dependent ferroptosis. In conclusion, energy stress promotes AMPK-mediated GPX4-dependent erastin-induced ferroptosis in renal cancer through the JAK2/STAT3/P53 signaling axis.
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spelling pubmed-95546642022-10-13 Energy-Stress-Mediated AMPK Activation Promotes GPX4-Dependent Ferroptosis through the JAK2/STAT3/P53 Axis in Renal Cancer Li, Yanze Zhang, Ye Qiu, Qiangmin Wang, Lei Mao, Hu Hu, Juncheng Chen, Zhiyuan Du, Yang Liu, Xiuheng Oxid Med Cell Longev Research Article Energy stress is an unfavorable condition that tumor cells are often exposed to. Ferroptosis is considered an emerging target for tumor therapy. However, the role of ferroptosis in energy stress in renal cancer is currently unknown. In this study, we found that glucose deprivation significantly enhanced GPX4-dependent ferroptosis through AMPK activation. Further, AMPK activation suppressed GPX4 expression at the transcriptional level through the upregulation of P53 expression. Additionally, the inactivation of JAK2/STAT3 transcriptionally promoted P53 expression, thereby promoting AMPK-mediated GPX4-dependent ferroptosis. In conclusion, energy stress promotes AMPK-mediated GPX4-dependent erastin-induced ferroptosis in renal cancer through the JAK2/STAT3/P53 signaling axis. Hindawi 2022-10-04 /pmc/articles/PMC9554664/ /pubmed/36246395 http://dx.doi.org/10.1155/2022/2353115 Text en Copyright © 2022 Yanze Li et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Yanze
Zhang, Ye
Qiu, Qiangmin
Wang, Lei
Mao, Hu
Hu, Juncheng
Chen, Zhiyuan
Du, Yang
Liu, Xiuheng
Energy-Stress-Mediated AMPK Activation Promotes GPX4-Dependent Ferroptosis through the JAK2/STAT3/P53 Axis in Renal Cancer
title Energy-Stress-Mediated AMPK Activation Promotes GPX4-Dependent Ferroptosis through the JAK2/STAT3/P53 Axis in Renal Cancer
title_full Energy-Stress-Mediated AMPK Activation Promotes GPX4-Dependent Ferroptosis through the JAK2/STAT3/P53 Axis in Renal Cancer
title_fullStr Energy-Stress-Mediated AMPK Activation Promotes GPX4-Dependent Ferroptosis through the JAK2/STAT3/P53 Axis in Renal Cancer
title_full_unstemmed Energy-Stress-Mediated AMPK Activation Promotes GPX4-Dependent Ferroptosis through the JAK2/STAT3/P53 Axis in Renal Cancer
title_short Energy-Stress-Mediated AMPK Activation Promotes GPX4-Dependent Ferroptosis through the JAK2/STAT3/P53 Axis in Renal Cancer
title_sort energy-stress-mediated ampk activation promotes gpx4-dependent ferroptosis through the jak2/stat3/p53 axis in renal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554664/
https://www.ncbi.nlm.nih.gov/pubmed/36246395
http://dx.doi.org/10.1155/2022/2353115
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