Molecular Mechanisms of Neutrophil Extracellular Traps in Promoting Gastric Cancer Epithelial–Mesenchymal Transition Through SERPINE‐1 Expression DOI Creative Commons
Zhen Ma, Xiaolin Li,

Shifeng Yang

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(3)

Published: March 1, 2025

Gastric cancer remains a significant global health concern, with its progression and metastasis often associated epithelial-mesenchymal transition (EMT). This study investigated the role of neutrophil extracellular traps (NETs) in promoting gastric EMT by regulating SERPINE-1 expression, which encodes plasminogen activator inhibitor-1 (PAI-1). Western blot immunohistochemistry were used to detect protein expression. Cell Counting Kit-8 was tested for cell proliferation ability using clones. The gene knocked down lentivirus. Immunofluorescence co-expression proteins, Transwell assay wound-healing investigate migration cells. Experimental conclusions verified vivo nude mouse model. We first demonstrated overexpression PAI-1 tissues lines. Subsequently, we found that NETs significantly enhanced expression EMT-related markers. These changes accompanied increases invasion, migration, tumour sphere formation. To further elucidate mechanism, employed lentivirus-mediated knockdown reverse NET-induced phenotype effectively. Mechanistically, activated transforming growth factor (TGF)-β signalling pathway via as evidenced increased TGF-β1, TGF-βR1, TGF-βR2, phosphorylated Smad2/3 Smad4. Finally, experiments model liver confirmed NET-treated HGC-27 cells exhibited metastatic potential abrogated potential. Our findings reveal novel mechanism promote PAI-1-TGF-β axis. can be target treatment cancer, is closely related prognosis patients cancer. Therapeutic strategies targeting or may help prevent improve clinical outcomes patients.

Language: Английский

Molecular Mechanisms of Neutrophil Extracellular Traps in Promoting Gastric Cancer Epithelial–Mesenchymal Transition Through SERPINE‐1 Expression DOI Creative Commons
Zhen Ma, Xiaolin Li,

Shifeng Yang

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(3)

Published: March 1, 2025

Gastric cancer remains a significant global health concern, with its progression and metastasis often associated epithelial-mesenchymal transition (EMT). This study investigated the role of neutrophil extracellular traps (NETs) in promoting gastric EMT by regulating SERPINE-1 expression, which encodes plasminogen activator inhibitor-1 (PAI-1). Western blot immunohistochemistry were used to detect protein expression. Cell Counting Kit-8 was tested for cell proliferation ability using clones. The gene knocked down lentivirus. Immunofluorescence co-expression proteins, Transwell assay wound-healing investigate migration cells. Experimental conclusions verified vivo nude mouse model. We first demonstrated overexpression PAI-1 tissues lines. Subsequently, we found that NETs significantly enhanced expression EMT-related markers. These changes accompanied increases invasion, migration, tumour sphere formation. To further elucidate mechanism, employed lentivirus-mediated knockdown reverse NET-induced phenotype effectively. Mechanistically, activated transforming growth factor (TGF)-β signalling pathway via as evidenced increased TGF-β1, TGF-βR1, TGF-βR2, phosphorylated Smad2/3 Smad4. Finally, experiments model liver confirmed NET-treated HGC-27 cells exhibited metastatic potential abrogated potential. Our findings reveal novel mechanism promote PAI-1-TGF-β axis. can be target treatment cancer, is closely related prognosis patients cancer. Therapeutic strategies targeting or may help prevent improve clinical outcomes patients.

Language: Английский

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