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能量应激介导的 AMPK 激活通过 JAK2/STAT3/P53 轴促进肾癌细胞中的 GPX4 依赖性铁死亡。

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

机构信息

Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei, China.

出版信息

Oxid Med Cell Longev. 2022 Oct 4;2022:2353115. doi: 10.1155/2022/2353115. eCollection 2022.

DOI:10.1155/2022/2353115
PMID:36246395
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9554664/
Abstract

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.

摘要

能量应激是肿瘤细胞经常面临的不利条件。铁死亡被认为是肿瘤治疗的一个新靶点。然而，铁死亡在肾癌中的能量应激中的作用目前尚不清楚。在这项研究中，我们发现葡萄糖剥夺通过 AMPK 激活显著增强了依赖 GPX4 的铁死亡。此外，AMPK 通过上调 P53 的表达在转录水平上抑制 GPX4 的表达。此外，JAK2/STAT3 的失活转录促进 P53 的表达，从而促进 AMPK 介导的依赖 GPX4 的 erastin 诱导的铁死亡。总之，能量应激通过 JAK2/STAT3/P53 信号通路促进 AMPK 介导的依赖 GPX4 的 erastin 诱导的铁死亡在肾癌中发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/d9de681a02fc/OMCL2022-2353115.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/db8060e2ccd6/OMCL2022-2353115.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/a4c67b6132fa/OMCL2022-2353115.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/9bc511e85255/OMCL2022-2353115.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/ee9fcc35481d/OMCL2022-2353115.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/a9f207dff7ff/OMCL2022-2353115.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/68c053e41405/OMCL2022-2353115.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/b2c62616f4a0/OMCL2022-2353115.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/d9de681a02fc/OMCL2022-2353115.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/db8060e2ccd6/OMCL2022-2353115.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/a4c67b6132fa/OMCL2022-2353115.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/9bc511e85255/OMCL2022-2353115.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/ee9fcc35481d/OMCL2022-2353115.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/a9f207dff7ff/OMCL2022-2353115.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/68c053e41405/OMCL2022-2353115.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/b2c62616f4a0/OMCL2022-2353115.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/9554664/d9de681a02fc/OMCL2022-2353115.008.jpg

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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
Vesicle-associated membrane protein 8 knockdown exerts anti-proliferative, pro-apoptotic, anti-autophagic, and pro-ferroptotic effects on colorectal cancer cells by inhibition of the JAK/STAT3 pathway.

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本文引用的文献

[1]
Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer.

Redox Biol. 2022-6

[2]
Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells.

Oxid Med Cell Longev. 2021

[3]
Emerging Roles of Energy Metabolism in Ferroptosis Regulation of Tumor Cells.

Adv Sci (Weinh). 2021-11

[4]
LSD1 Promotes Prostate Cancer Cell Survival by Destabilizing FBXW7 at Post-Translational Level.

Front Oncol. 2021-2-23

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STAT3 and p53: Dual Target for Cancer Therapy.

Biomedicines. 2020-12-21

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Energy metabolism as a regulator of ferroptosis.

Cell Cycle. 2020-11

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LKB1-AMPK axis negatively regulates ferroptosis by inhibiting fatty acid synthesis.

Signal Transduct Target Ther. 2020-9-3

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Warburg and Beyond: The Power of Mitochondrial Metabolism to Collaborate or Replace Fermentative Glycolysis in Cancer.

Cancers (Basel). 2020-4-30

[9]
Ferroptosis and Its Potential Role in Human Diseases.

Front Pharmacol. 2020-3-17

[10]
Energy-stress-mediated AMPK activation inhibits ferroptosis.

Nat Cell Biol. 2020-2-6

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