Programming a Ferroptosis‐to‐Apoptosis Transition Landscape Revealed Ferroptosis Biomarkers and Repressors for Cancer Therapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(17)

Published: March 5, 2024

Abstract Ferroptosis and apoptosis are key cell‐death pathways implicated in several human diseases including cancer. is driven by iron‐dependent lipid peroxidation currently has no characteristic biomarkers or gene signatures. Here a continuous phenotypic gradient between ferroptosis coupled to transcriptomic metabolomic landscapes established. The gradual ferroptosis‐to‐apoptosis landscape used generate unique, unbiased predictor, the Gradient Gene Set (GGS), which classified with high accuracy. Further GGS optimization using multiple ferroptotic apoptotic datasets revealed highly specific biomarkers, robustly validated vitro vivo. A subset of associated poor prognosis breast cancer patients PDXs contains different repressors. Depletion one representative, PDGFA‐assaociated protein 1(PDAP1), found suppress basal‐like tumor growth mouse model. Omics mechanistic studies that enhanced lysosomal function, glutaminolysis, tricarboxylic acid (TCA) cycle, while its transition into attributed endoplasmic reticulum(ER)‐stress phosphatidylethanolamine (PE)‐to‐phosphatidylcholine (PC) metabolic shift. Collectively, this study highlights molecular mechanisms underlying execution, identified predictive signature prognostic value, versus repressors for therapy.

Language: Английский

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Self-assembled nanodrug based on ferroptosis inducer and sonosensitizer for enhanced sonodynamic-triggered multimodal synergistic therapy of prostate cancer

European Journal of Pharmaceutics and Biopharmaceutics, Journal Year: 2025, Volume and Issue: 208, P. 114656 - 114656

Published: Feb. 3, 2025

Language: Английский

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A snapshot into the transcriptomic landscape of apoptosis and ferroptosis in cancer

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(5)

Published: May 29, 2024

Apoptosis and ferroptosis are two regulated cell death (RCD) pathways implicated in different human diseases considered as promising strategies to eliminate cancer cells. These characterized by distinct morphological biochemical properties, induce through mechanisms, but share common regulators types. Although apoptosis have been extensively studied over the last few years, their transcriptomic responses not yet systematically compared due remarkable variability data. Here we provide a brief snapshot of landscapes cancer, discuss divergent convergent implications therapy.

Language: Английский

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Potential applications of gene expression profiles obtained from circulating extracellular vesicles in breast cancer.

The Journal of Liquid Biopsy, Journal Year: 2025, Volume and Issue: 7, P. 100287 - 100287

Published: Jan. 19, 2025

Liquid biopsy-based biomarkers offer several advantages since they are minimally invasive, can be useful in longitudinal monitoring of the disease and have higher patient compliance. We describe a protocol using minimal volumes archival prospective serum/plasma samples to define RNA contents EVs discuss its benefits limitations. RNA-seq analysis matched tumor biopsy, circulating from breast cancer patients (EV-C, n = 26) healthy donors (EV-H, 4) was performed differentially expressed genes were validated by RT-PCR separate series 32 EV-H, 22). A total 84 studied. data 500 μl serum yielded more than 17000 genes, which 320 DEGs (adjusted p value ≤ 0.05) between EV-C EV-H samples. Pathways for Myc V1, reactive oxygen species, angiogenesis, allograft rejection Interferon regulated over-represented Computational deconvolution algorithms cell signatures identified immune cells such as Th1 memory T-cells, endothelial cells, osteoblasts stromal compartment significant. Top 6 qRT-PCR all (n 84) consistently correctly classified groups. An independent set 374 640 could segregate ER positive/ER negative non-metastatic versus metastatic samples, respectively. had variability gene expression patterns whereas those showed better correlation. By low amounts successfully EV transcriptomics, we demonstrate that invasive technique converted microinvasive format. These lay foundation based biomarker discovery segregating cancers.

Language: Английский

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CHAC1 Mediates Endoplasmic Reticulum Stress‐Dependent Ferroptosis in Calcium Oxalate Kidney Stone Formation

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Abstract The initiation of calcium oxalate (CaOx) kidney stone formation is highly likely to stem from injury the renal tubular epithelial cells (RTECs) induced by stimulation an aberrant urinary environment. CHAC1 plays a critical role in stress response mechanisms regulating glutathione metabolism. Endoplasmic reticulum (ER) and ferroptosis are demonstrated be involved formation. This study attempted elucidate mechanism ER stress‐dependent CaOx stones. Here, expression performed vivo vitro models. These findings indicated that 4‐Phenylbutyric acid (4‐PBA)treatment deficiency alleviated ferroptotic status, including restoring GSH content, suppressing Fe 2+ lipid peroxidation accumulation, as well ferroptosis‐related proteins. Notably, 4‐PBA treatment both attenuated oxidative damage, improved function, importantly, decreased crystal deposition. Additionally, ChIP‐seq ChIP‐qPCR analyses vital downstream target gene ATF4. results ATF4 depletion inhibited upregulation pro‐ferroptotic Ox stimulation. Overall, ATF4/CHAC1 axis mediating may promising research direction for identifying potential strategy prevent treat

Language: Английский

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Broadening horizons: research on ferroptosis in lung cancer and its potential therapeutic targets

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 23, 2025

Ferroptosis is a novel form of cell death distinct from traditional mechanisms, characterized by the accumulation iron ions and production lipid peroxides. It not only affects survival tumor cells but also closely linked to changes in microenvironment. Lung cancer one leading malignancies worldwide terms incidence mortality, its complex biological mechanisms resistance make treatment challenging. Recent studies have shown that ferroptosis plays key role onset progression lung cancer, with intricate regulatory influencing development response therapy. As research into deepens, related molecular pathways, such as glutamate metabolism, antioxidant defense, been gradually revealed. However, clinical practice, ferroptosis-based therapeutic strategies for are still their early stages. Challenges remain, including incomplete understanding specific ferroptosis, insufficient on factors, limited insight interactions within Therefore, effective modulation enhance remains an urgent issue. This review summarizes analyzes factors interaction microenvironment, further explores potential targeting ferroptosis. By synthesizing latest research, this paper aims provide new perspectives directions treatment, goal advancing applications.

Language: Английский

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Ferroptosis Inducer RSL3 Inhibits Cell Death by Camptothecin-Induced Apoptosis

Journal of Biophysical Chemistry, Journal Year: 2025, Volume and Issue: 16(01), P. 1 - 13

Published: Jan. 1, 2025

Language: Английский

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Endoplasmic reticulum stress-autophagy axis is involved in copper-induced ovarian ferroptosis

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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A nuclei bombing nano-system improves STING-activated cancer immunotherapy

Nano Today, Journal Year: 2025, Volume and Issue: 63, P. 102749 - 102749

Published: April 7, 2025

Language: Английский

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Recommendations for robust and reproducible research on ferroptosis

Nature Reviews Molecular Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Language: Английский

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