Targeting ferroptosis as a vulnerability in cancer

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(7), P. 381 - 396

Published: March 25, 2022

Language: Английский

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Mitochondrial regulation of ferroptosis

The Journal of Cell Biology, Journal Year: 2021, Volume and Issue: 220(9)

Published: July 30, 2021

Ferroptosis is a form of iron-dependent regulated cell death driven by uncontrolled lipid peroxidation. Mitochondria are double-membrane organelles that have essential roles in energy production, cellular metabolism, and regulation. However, their role ferroptosis has been unclear somewhat controversial. In this Perspective, I summarize the diverse metabolic processes mitochondria actively drive ferroptosis, discuss recently discovered mitochondria-localized defense systems detoxify mitochondrial peroxides protect against present new evidence for regulating outline outstanding questions on fascinating topic future investigations. An in-depth understanding functions will important implications both fundamental biology disease treatment.

Language: Английский

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A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 22, 2022

Targeting ferroptosis, a unique cell death modality triggered by unrestricted lipid peroxidation, in cancer therapy is hindered our incomplete understanding of ferroptosis mechanisms under specific genetic contexts. KEAP1 (kelch-like ECH associated protein 1) frequently mutated or inactivated lung cancers, and mutant cancers are refractory to most therapies, including radiotherapy. In this study, we identify suppressor 1 (FSP1, also known as AIFM2) transcriptional target nuclear factor erythroid 2-related 2 (NRF2) reveal that the ubiquinone (CoQ)-FSP1 axis mediates ferroptosis- radiation- resistance deficient cells. We further show pharmacological inhibition CoQ-FSP1 sensitizes cells patient-derived xenograft tumors radiation through inducing ferroptosis. Together, study identifies key downstream effector KEAP1-NRF2 pathway potential therapeutic for treating cancers.

Language: Английский

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GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(3), P. 188890 - 188890

Published: March 29, 2023

Language: Английский

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SLC7A11 regulated by NRF2 modulates esophageal squamous cell carcinoma radiosensitivity by inhibiting ferroptosis

Journal of Translational Medicine, Journal Year: 2021, Volume and Issue: 19(1)

Published: Aug. 26, 2021

Abstract Background Solute carrier family 7 member 11(SLC7A11) is a component of cysteine/glutamate transporter, which plays key role in tumor growth; however, its underlying effect on radiosensitivity esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to clarify SLC7A11’s expression and correlation with nuclear factor erythroid-2 ( NRF2)-associated radioresistance ESCC. Methods We included 127 ESCC patients who received radical chemoradiotherapy. Immunohistochemical staining was used detect SLC7A11 NRF2 expression, the relationship between clinicopathological characteristics survival rates or therapy response were evaluated. Western blot, dual-reporter assays Chromatin immunoprecipitation (ChIP)-sequencing analyze their vitro. Their roles then investigated through multiple validation steps. Results overexpressed tissues positively correlated one another. significantly associated length, lymph node metastasis, TNM stage, while metastasis. Patients high had shorter overall progression-free survival, poor treatment response. The multivariate model showed that sex location are independent prognostic factors. In vitro analysis confirmed hyperactivation induced by directly binding promoter region, promoting radioresistance, reducing radiotherapy-induced lipid peroxidation levels, PTGS2 radiotherapy-related ferroptosis morphologic features. Conclusion Our reveals connection related worse poorer outcomes. SLC7A11-mediated inhibition NRF2-associated highlighting potential NRF2/SLC7A11/ferroptosis axis as future therapeutic targets against resistance biomarker.

Language: Английский

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Overcoming cancer chemotherapy resistance by the induction of ferroptosis

Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 66, P. 100916 - 100916

Published: Dec. 29, 2022

Language: Английский

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Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Language: Английский

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Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx

Journal of Advanced Research, Journal Year: 2022, Volume and Issue: 41, P. 63 - 75

Published: Jan. 11, 2022

Excessive mechanical stress is closely associated with cell death in various conditions. Exposure of chondrocytes to excessive loading leads a catabolic response as well exaggerated death. Ferroptosis recently identified form during aging and degeneration. However, it's potential association remains be illustrated.To identify whether can cause ferroptosis. To explore the role overloading chondrocyte ferroptosis.Chondrocytes were collected from unloading zones cartilage patients osteoarthritis (OA), ferroptosis phenotype was analyzed through transmission electron microscope microarray. Moreover, relationship between OA by GPX4-conditional knockout (Col2a1-CreERT: GPX4flox/flox) mice model cultured high strain stress. Furthermore, Piezo1 ion channel development explored using its inhibitor (GsMTx4) agonist (Yoda1). Additionally, calcium-free medium stress, tested.Human mouse experiments revealed that induce GPX4-associated Conditional GPX4 aggravated experimental process, while additional treatment suppressor protein (FSP-1) coenzyme Q10 (CoQ10) abated GPX4-CKO mice. In experiments, inhibition activity increased expression, attenuated reduced severity osteoarthritis. induced damage largely abolished blocking calcium influx medium.Our findings show induces activation subsequent chondrocytes, which might provide target for treatment.

Language: Английский

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The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(4), P. 513 - 534

Published: April 1, 2024

Language: Английский

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Construction of Fe-doped ZIF-8/DOX nanocomposites for ferroptosis strategy in the treatment of breast cancer

Journal of Materials Chemistry B, Journal Year: 2023, Volume and Issue: 11(27), P. 6335 - 6345

Published: Jan. 1, 2023

The DOX@7FZ was able to enhance the ROS level in cancer cells via a synergistic effect between apoptosis/ferroptosis synergism.

Language: Английский

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