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, Yanwei; Liu, Xiuheng

doi:10.1155/2022/2353115

Cited by 19 publications

(10 citation statements)

References 41 publications

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“…When activated, AMPK inhibited JAK2 and STAT3 phosphorylation, increased p53 expression, and decreased GPX4 expression, thereby contributing to the promotion of ferroptosis in renal cancer. 32 The activated JAK2/STAT3 pathway induces TGF-β1 secretion from tumor-associated macrophages (TAMs), which in turn activates HLF-GGT1 axis and ultimately contributes to ferroptosis resistance, proliferation, metastasis, and chemotherapy resistance of TNBC cells. 33 FANCD2 acted as a tumor suppressor by reducing JAK2 and STAT3 phosphorylation, hindering osteosarcoma cell proliferation and inducing ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

“…JAK2/STAT3 pathway is a signaling pathway involved in ferroptosis that has been studied more in recent years. When activated, AMPK inhibited JAK2 and STAT3 phosphorylation, increased p53 expression, and decreased GPX4 expression, thereby contributing to the promotion of ferroptosis in renal cancer 32 . The activated JAK2/STAT3 pathway induces TGF‐β1 secretion from tumor‐associated macrophages (TAMs), which in turn activates HLF‐GGT1 axis and ultimately contributes to ferroptosis resistance, proliferation, metastasis, and chemotherapy resistance of TNBC cells 33 .…”

Section: Discussionmentioning

confidence: 99%

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Erianin inhibits tumor growth by promoting ferroptosis and inhibiting invasion in hepatocellular carcinoma through the JAK2/STAT3/SLC7A11 pathway

Chen,

Sun,

Fang

2024

Pathology International

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Iron has been found to be involved in the tumor cell proliferation process, which can lead to the increased sensitivity of cancer cells to ferroptosis. Since erianin is associated with oxidative stress in hepatocellular carcinoma (HCC), we hypothesized that the therapeutic effect and mechanism of erianin on HCC is related to ferroptosis. HCC cells were stimulated with increase of erianin concentrations for 24 h, and the survival rates of Huh‐7 and HepG2 cells gradually decreased. After intervention with different doses of erianin, cell proliferation, clone number, and invasion were prominently decreased, apoptosis ratio was increased. Moreover, Nec‐1, CQ, and Z‐VAD had no effect on the cell viability induced by erianin, while the combination of ferroptosis inhibitors (deferoxamine mesylate, ferrostatin‐1, and liproxstatin‐1) and erianin prominently increased cell survival rate. Erianin pretreatment induced ferroptosis by enhancing reactive oxygen species, MDA, and Fe2+ levels, and reducing GSH levels. Erianin activated JAK2/STAT3 pathway and inhibited SLC7A11 and GPX4 expression, thereby inducing ferroptosis. Besides, tumor growth was significantly inhibited in the erianin‐treated mice, and there was no obvious toxicity in the mice. Erianin reduced proliferation and invasion of HCC cells by inducing ferroptosis by blocking the JAK2/STAT3/SLC7A11 pathway, thereby impeding tumor growth.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Erianin inhibits tumor growth by promoting ferroptosis and inhibiting invasion in hepatocellular carcinoma through the JAK2/STAT3/SLC7A11 pathway

Chen,

Sun,

Fang

2024

Pathology International

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“…Studies have demonstrated that a GPX4-dependent cancer cell state underpins clear-cell morphology and imparts ferroptosis sensitivity [74]. Li et al [75] revealed that energy-stress-mediated AMPK activation promoted GPX4-dependent ferroptosis in renal cancer by way of the JAK2/STAT3/P53 axis. Another study demonstrated that ether lipid plasticity enhanced ferroptosis susceptibility and evasion [76].…”

Section: Ferroptosis and Kidney Diseasesmentioning

confidence: 99%

Novel Insight into Ferroptosis in Kidney Diseases

Liu¹,

Liu²,

Zhou³

et al. 2023

Am J Nephrol

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Background: Various kidney diseases such as acute kidney injury, chronic kidney disease, polycystic kidney disease, renal cancer, and kidney stones, are an important part of the global burden, bringing a huge economic burden to people around the world. Ferroptosis is a type of nonapoptotic iron-dependent cell death caused by the excess of iron-dependent lipid peroxides and accompanied by abnormal iron metabolism and oxidative stress. Over the past few decades, several studies have shown that ferroptosis is associated with many types of kidney diseases. Studying the mechanism of ferroptosis and related agonists and inhibitors may provide new ideas and directions for the treatment of various kidney diseases. Summary: In this review, we discuss the differences between ferroptosis and other types of cell death such as apoptosis, necroptosis, pyroptosis, cuprotosis, pathophysiological features of the kidney, and ferroptosis-induced kidney injury. We also provide an overview of the molecular mechanisms involved in ferroptosis and events that lead to ferroptosis. Furthermore, we summarize the possible clinical applications of this mechanism among various kidney diseases. Key Message: The current research suggests that future therapeutic efforts to treat kidney ailments would benefit from a focus on ferroptosis.

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“…Previous studies have shown that the transcription factors such as stem cell factor (SOX2), BTB and CNC homology 1 (BACH1) play important roles in ferroptosis of cancer cells [29,30]. The signal transduction and activators of transcription 3 (STAT3)-mediated ferroptosis regulate the progression of PCa and kidney cancer [31,32]. Recently, lncRNAs have been reported to involve in heavy metals induced cancer development.…”

Section: Frlncrnas Regulates Genes Through Transcription Factors and ...mentioning

confidence: 99%

The Roles of Ferroptosis-related Long Non-coding RNAs in Urologic Cancers

Xie

Qin

et al. 2023

ann urol oncol

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Ferroptosis is a type of programmed cell death that has been recent topic of interest in cancer therapy. Growing evidence indicates that long noncoding RNAs (lncRNAs) are involved in ferroptosis and associated with the incidence and progression of cancer. However, the relationship between lncRNA and ferroptosis in urologic cancers has not been fully elucidated. In this review, we summarize ferroptosis-related lncRNAs (frlncRNAs) in urologic cancers. Studies indicate that frlncRNAs are associated with cancer metabolism, tumor microenvironment, and immune cell infiltration. In addition, frlncRNAs could regulate ferroptosis related genes both at the mRNA and protein level. Therefore, a deep understanding of the roles of frlncRNAs in urologic cancers occurrence and progression will provide novel information for the development of anticancer therapies.

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

Cited by 19 publications

References 41 publications

Erianin inhibits tumor growth by promoting ferroptosis and inhibiting invasion in hepatocellular carcinoma through the JAK2/STAT3/SLC7A11 pathway

Erianin inhibits tumor growth by promoting ferroptosis and inhibiting invasion in hepatocellular carcinoma through the JAK2/STAT3/SLC7A11 pathway

Novel Insight into Ferroptosis in Kidney Diseases

The Roles of Ferroptosis-related Long Non-coding RNAs in Urologic Cancers

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