The redox protein HMGB1 in cell death and cancer

Chen, Ruochan; Zou, Jiong; Kang, Rui; Tang, Doalin

doi:10.1089/ars.2023.0007

Cited by 16 publications

(16 citation statements)

References 87 publications

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“…In addition, we determined the serum levels of HMGB‐1, a major kind of DAMP released by cuproptotic cells. [ 32 ] Enzyme‐linked immunosorbent assays (ELISAs) confirmed that the ES@CuO‐treated mice released a large amount of HMGB‐1 into the extracellular space (Figure S16 , Supporting Information). Taken together, these results indicated that ES@CuO‐induced cuproptosis could inhibit tumor growth in vivo.…”

Section: Resultsmentioning

confidence: 97%

Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy

Lu,

Chen,

Lin

et al. 2024

Advanced Science

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The induction of cuproptosis, a recently identified form of copper‐dependent immunogenic cell death, is a promising approach for antitumor therapy. However, sufficient accumulation of intracellular copper ions (Cu2+) in tumor cells is essential for inducing cuproptosis. Herein, an intelligent cuproptosis‐inducing nanosystem is constructed by encapsulating copper oxide (CuO) nanoparticles with the copper ionophore elesclomol (ES). After uptake by tumor cells, ES@CuO is degraded to release Cu2+ and ES to synergistically trigger cuproptosis, thereby significantly inhibiting the tumor growth of murine B16 melanoma cells. Moreover, ES@CuO further promoted cuproptosis‐mediated immune responses and reprogrammed the immunosuppressive tumor microenvironment by increasing the number of tumor‐infiltrating lymphocytes and secreted inflammatory cytokines. Additionally, combining ES@CuO with programmed cell death‐1 (PD‐1) immunotherapy substantially increased the antitumor efficacy in murine melanoma. Overall, the findings of this study can lead to the use of a novel strategy for cuproptosis‐mediated antitumor therapy, which may enhance the efficacy of immune checkpoint inhibitor therapy.

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Section: Resultsmentioning

confidence: 97%

Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy

Lu,

Chen,

Lin

et al. 2024

Advanced Science

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“…Therefore, BMAL1 emerges as a potential target in investigating tumor therapeutic strategies aimed at ferroptosis. HMGB1 plays a role in various diseases and pathological processes (Chen et al 2023b , a ). Moreover, HMGB1 also plays an important role in autophagy.…”

Section: Discussionmentioning

confidence: 99%

“…BECN1, a BH3-only protein, forms a complex with other proteins to promote the formation of autophagic vesicles, thereby initiating autophagy (Dikic et al 2018 ). HMGB1 has multiple functions, and the functions of HMGB1 vary depending on its subcellular localization (Chen et al 2023b , a ). Cytosolic HMGB1 can bind to BECN1, inducing autophagosome formation and promoting autophagy (Kang et al 2010 ; Tang et al 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Targeting BMAL1 reverses drug resistance of acute myeloid leukemia cells and promotes ferroptosis through HMGB1-GPX4 signaling pathway

Zheng,

Wu,

Lin

et al. 2024

J Cancer Res Clin Oncol

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Purpose Acute myeloid leukemia (AML) is a refractory hematologic malignancy that poses a serious threat to human health. Exploring alternative therapeutic strategies capable of inducing alternative modes of cell death, such as ferroptosis, holds great promise as a viable and effective intervention. Methods We analyzed online database data and collected clinical samples to verify the expression and function of BMAL1 in AML. We conducted experiments on AML cell proliferation, cell cycle, ferroptosis, and chemotherapy resistance by overexpressing/knocking down BMAL1 and using assays such as MDA detection and BODIPY 581/591 C11 staining. We validated the transcriptional regulation of HMGB1 by BMAL1 through ChIP assay, luciferase assay, RNA level detection, and western blotting. Finally, we confirmed the results of our cell experiments at the animal level. Results BMAL1 up-regulation is an observed phenomenon in AML patients. Furthermore, there existed a strong correlation between elevated levels of BMAL1 expression and inferior prognosis in individuals with AML. We found that knocking down BMAL1 inhibited AML cell growth by blocking the cell cycle. Conversely, overexpressing BMAL1 promoted AML cell proliferation. Moreover, our research results revealed that BMAL1 inhibited ferroptosis in AML cells through BMAL1-HMGB1-GPX4 pathway. Finally, knocking down BMAL1 can enhance the efficacy of certain first-line cancer therapeutic drugs, including venetoclax, dasatinib, and sorafenib. Conclusion Our research results suggest that BMAL1 plays a crucial regulatory role in AML cell proliferation, drug resistance, and ferroptosis. BMAL1 could be a potential important therapeutic target for AML.

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“…For example, a bioinformatics analysis of osteosarcoma patients utilizing the Cancer Genome Atlas database unveiled a 4‐gene panel (WASP actin nucleation promoting factor [ WAS ], cortistatin [ CORT ], Wnt family member 16 [ WNT16 ], and galactosidase beta 1 like 2 [ GLB1L2 ]) as biomarkers associated with both ferroptosis and immune response in the tumor microenvironment 109 . Furthermore, the redox status of HMGB1 released during cell death, such as ferroptosis, has the potential to shift the antitumor response from immunostimulation to immunosuppression 110 …”

Section: Immune Consequence: Dual Role Of Ferroptosismentioning

confidence: 99%

Ferroptosis in immunostimulation and immunosuppression

Tang

Kroemer

Kang

2023

Immunological Reviews

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SummaryFerroptosis is a form of iron‐dependent regulated cell death characterized by the accumulation of toxic lipid peroxides, particularly in the plasma membrane, leading to lytic cell death. While it plays a crucial role in maintaining the overall health and proper functioning of multicellular organisms, it can also contribute to tissue damage and pathological conditions. Although ferroptotic damage is generally recognized as an immunostimulatory process associated with the release of damage‐associated molecular patterns (DAMPs), the occurrence of ferroptosis in immune cells or the release of immunosuppressive molecules can result in immune tolerance. Consequently, there is ongoing exploration of targeting the upstream signals or the machinery of ferroptosis to therapeutically enhance or inhibit the immune response. In addition to introducing the core molecular mechanisms of ferroptosis, we will focus on the immune characteristics of ferroptosis in pathological conditions, particularly in the context of infection, sterile inflammation, and tumor immunity.

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The redox protein HMGB1 in cell death and cancer

Cited by 16 publications

References 87 publications

Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy

Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy

Targeting BMAL1 reverses drug resistance of acute myeloid leukemia cells and promotes ferroptosis through HMGB1-GPX4 signaling pathway

Ferroptosis in immunostimulation and immunosuppression

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