Molecular Mechanisms of Neutrophil Extracellular Traps in Promoting Gastric Cancer Epithelial–Mesenchymal Transition Through SERPINE‐1 Expression

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

Exploring the Role of Cellular Interactions in the Colorectal Cancer Microenvironment

Journal of Immunology Research, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Colorectal cancer (CRC) stands as one of the tumors with globally high incidence and mortality rates. In recent years, researchers have extensively explored role tumor immune microenvironment (TME) in CRC, highlighting crucial influence cell populations driving progression shaping therapeutic outcomes. The TME encompasses an array cellular noncellular constituents, spanning cells, myeloid tumor-associated fibroblasts, among others. However, composition within is highly dynamic, evolving throughout different stages progression. These shifts subpopulation proportions lead to a gradual transition response, shifting from early antitumor growth late-stage environment that supports survival. Therefore, it further investigate understand complex interactions various TME. this review, we explore key components varying origins, subpopulations shared elements CRC TME, examining their interconnections critical considerations for developing personalized precise immunotherapy strategies.

Language: Английский