Elevated neutrophil extracellular traps by HBV‐mediated S100A9‐TLR4/RAGE‐ROS cascade facilitate the growth and metastasis of hepatocellular carcinoma

Zhan, Xi; Wu, Rui; Kong, Xuehua; You, Yan; He, Kun; Sun, Xiaoyu; Huang, Yong; Chen, Weixian; Duan, Liang

doi:10.1002/cac2.12388

Cited by 40 publications

(35 citation statements)

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“…Reported mechanisms include that S100A9 enhances cancer stem-like properties of hepatocellular carcinoma [ 42 ]. Activation of RAGE/TLR4-ROS signaling pathway leads to the formation of Neutrophil extracellular traps (NETs) that promote HCC growth and metastasis [ 43 ]. Depletion or pharmacological inhibition of S100A9 significantly inhibited HCC growth and metastasis ability [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Characteristic of molecular subtypes based on PANoptosis-related genes and experimental verification of hepatocellular carcinoma

Ren

Kang

Yin

et al. 2023

Aging

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Hepatocellular carcinoma (HCC) is a type of liver cancer that originates from liver cells. It is one of the most common types of liver cancer and a leading cause of cancer-related death worldwide. Early detection and treatment can improve the HCC prognosis. Therefore, it is necessary to further improve HCC markers and risk stratification. PANoptosome is a cytoplasmic polymer protein complex that regulates a proinflammatory programmed cell death pathway called “PANoptosis”. The role of PANoptosis in HCC remains unclear. In this study, the molecular changes of PANoptosis related genes (PAN-RGs) in HCC were systematically evaluated. We characterized the heterogeneity of HCC by using consensus clustering to identify two distinct subtypes. The two subtypes showed different survival rate, biological function, chemotherapy drug sensitivity and immune microenvironment. After identification of PAN-RG differential expression genes (DEGs), a prognostic model was established by Cox regression analysis using minimum absolute contraction and selection operator (LASSO), and its prognostic value was verified by Cox regression analysis, Kaplan-Meier curve and receiver operating characteristic (ROC) curve. Our own specimens were also used to further validate the prognostic significance and possible clinical value of the selected targets. Subsequently, we conducted a preliminary discussion on the reasons for the influence of the model on the prognosis through TME analysis, drug resistance analysis, TMB analysis and other studies. This study provides a new idea for individualized and precise treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

Characteristic of molecular subtypes based on PANoptosis-related genes and experimental verification of hepatocellular carcinoma

Ren

Kang

Yin

et al. 2023

Aging

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“…Despite the fact that PI3Kγ is involved in regulating NETs formation during AAA, the molecular mechanism is still poorly understood. Previous studies have shown that reactive oxygen species (ROS) is an important inducer regulating the formation of NETs 45 , and NADPH oxidase enzyme 2 (NOX2) is the key enzyme that produces ROS to mediate the formation of NETs 46 . However, our data showed that PI3Kγ blockade reduced the expression of NETs, but not decreased the upregulation of NOX2 upon LPS stimulation, and had a synergistic effect when combined with NOX2 inhibitor.…”

Section: Discussionmentioning

confidence: 99%

PI3Kgamma promotes neutrophil extracellular trap formation by noncanonical pyroptosis in abdominal aortic aneurysm

Xiong,

Liu,

Liu

et al. 2024

Preprint

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Background: Abdominal aortic aneurysm (AAA) is one of the most life-threatening cardiovascular diseases while currently lacks effective drug treatment. NETs formation has been proved to be crucial trigger of AAA, so finding its upstream regulatory targets is the key to discovering therapeutic agents for AAA. Methods and Results: we reveal that PI3Kγ (PI3Kγ) is an upstream signal that regulates NETs formation. Inhibition of PI3K? reduces the expression of NETs and reduces inflammation in the aortic wall, thereby significantly ameliorating AAA. However, the mechanism of NETs formation regulated by PI3Kγ has not been fully elucidated. Using isolated bone marrow neutrophils, we show that PI3Kγ deficiency inactivates the noncanonical pyroptosis pathway (Capase11/GSDMD) to inhibit NETs expression, and subsequently found that PI3Kγ regulation of noncanonical pyroptosis via anchoring PKA is dependent on cAMP/PKA signaling, but not on classical PI3K/AKT signaling. Conclusions: Our research uncovers the role and mechanism of PI3Kγ in AAA development and provides insights into AAA therapy from the perspective of NETs formation.

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“…Neutrophil extracellular traps enable to elicit filopodia formation and cell motility in CRC cells dependent upon the activation of EMT process, eventually resulting in the metastatic development of CRC 55 . Neutrophil extracellular traps facilitate the growth and metastasis of HCC, which are primarily dominated by enhanced angiogenesis, EMT‐associated cell migration, matrix metalloproteinases (MMPs)‐based extracellular matrix (ECM) degradation, and NET‐elicited cell trapping 56 . Inhibiting NET production by DNase I potently abrogates the NETs‐evoked HCC growth and metastasis.…”

Section: Netosis In Cancer Metastasismentioning

confidence: 99%

NETosis: Sculpting tumor metastasis and immunotherapy

Hu,

Wang,

Liu

2023

Immunological Reviews

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SummaryThe process of neutrophil extracellular traps (NETs) formation, called NETosis, is a peculiar death modality of neutrophils, which was first observed as an immune response against bacterial infection. However, recent work has revealed the unique biology of NETosis in facilitating tumor metastatic process. Neutrophil extracellular traps released by the tumor microenvironment (TME) shield tumor cells from cytotoxic immunity, leading to impaired tumor clearance. Besides, tumor cells tapped by NETs enable to travel through vessels and subsequently seed distant organs. Targeted ablation of NETosis has been proven to be beneficial in potentiating the efficacy of cancer immunotherapy in the metastatic settings. This review outlines the impact of NETosis at almost all stages of tumor metastasis. Furthermore, understanding the multifaceted interplay between NETosis and the TME components is crucial for supporting the rational development of highly effective combination immunotherapeutic strategies with anti‐NETosis for patients with metastatic disease.

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Elevated neutrophil extracellular traps by HBV‐mediated S100A9‐TLR4/RAGE‐ROS cascade facilitate the growth and metastasis of hepatocellular carcinoma

Cited by 40 publications

References 50 publications

Characteristic of molecular subtypes based on PANoptosis-related genes and experimental verification of hepatocellular carcinoma

Characteristic of molecular subtypes based on PANoptosis-related genes and experimental verification of hepatocellular carcinoma

PI3Kgamma promotes neutrophil extracellular trap formation by noncanonical pyroptosis in abdominal aortic aneurysm

NETosis: Sculpting tumor metastasis and immunotherapy

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