Fusobacterium nucleatum promotes colorectal cancer liver metastasis via miR-5692a/IL-8 axis by inducing epithelial-mesenchymal transition

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 6, 2025

Abstract Background The association between the intestinal microbiota and colorectal cancer (CRC) has been extensively studied, with Fusobacterium nucleatum ( F. , FN) being found in high abundance tissues. Previous research emphasized significant role of occurrence CRC. However, impact on CRC liver metastasis not well understood. Methods effects ability cell were evaluated vitro examined by wound-healing assay transwell assay. mouse model was constructed spleen injection, degree assessed vivo bioluminescence imaging. gene expression changes cells after co-culture analyzed through transcriptome sequencing. qRT-PCR Western Blot assays performed to validate related genes proteins. Results significantly enhanced vitro. In model, also promoted development Mechanistically, infection increased IL-8 downregulated level miR-5692a, a regulatory microRNA IL-8. This led activation ERK pathway resulted epithelial-mesenchymal transition (EMT) cells. Conclusions Our results suggest that promotes inducing miR-5692a/IL-8 axis. These findings provide new insights for prevention treatment metastasis.

Language: Английский

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Extracellular fluid viscosity regulates human mesenchymal stem cell lineage and function

Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

Human mesenchymal stem cells (hMSCs) respond to mechanical stimuli, including stiffness and viscoelasticity. To date, it is unknown how extracellular fluid viscosity affects hMSC function on substrates of different While hMSCs assume an adipogenic phenotype gels low prescribed stress relaxation times, elevated sufficient bias toward osteogenic phenotype. Elevated induces Arp2/3-dependent actin remodeling, enhances NHE1 activity, promotes spreading via up-regulation integrin-linked kinase. The resulting increase in membrane tension triggers the activation transient receptor potential cation vanilloid 4 facilitate calcium influx, thereby stimulating RhoA/ROCK driving YAP-dependent RUNX2 translocation nucleus, leading differentiation. soft at relative basal favor M2 macrophage This study establishes as a key physical cue that imprints memory immunosuppressive

Language: Английский

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Effects of macrophages in OSCC progression

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Macrophages are crucial immune cells within the tumor microenvironment (TME), involved in regulating proliferation, invasion, metastasis, ECM remodeling, angiogenesis, and immunosuppression. Although more experimental evidence clinical data indicate that macrophages onset progression of oral squamous cell carcinoma (OSCC), exact pathogenesis OSCC associated with has not been fully elucidated. Enhanced knowledge molecular mechanisms involving will aid creation treatments targeted specifically at macrophages. This review outlines pro-tumoral anti-tumoral effects OSCC, emphasizing interaction between It can provide theoretical basis for establishment complex regulatory network centered on explore novel therapeutic strategies OSCC.

Language: Английский

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Piezo1 promotes vibration-induced vascular smooth muscle injury by regulating the NF-κB/p65 axis

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 21, 2025

Vibration induced damage to the peripheral circulatory system is thought be an early stage of hand-arm vibration syndrome (HAVS) caused by occupational exposure hand-transmitted (HTV). This study investigated mechanisms underlying vibration-induced vascular injury, focusing on role Piezo1, a mechanosensitive channel, and its association with NF-κB/p65 signaling pathway. We demonstrated that leads Piezo1-mediated upregulation angiogenic chemokines, including CCL2, CCL5, CXCL1, CXCL2, CXCL10, through To mimic effects vibration, rat model cellular were used. Animal models showed dysfunction while increasing Piezo1 expression. knockdown or p65 inhibition attenuated these effects, suggesting crucial for Piezo1-NF-κB/p65 axis in dysfunction. Furthermore, chemokines identified as potential biomarkers diagnosis HAVS occupationally exposed individuals. These results highlight pathway therapeutic targets underscore need further validation human samples exploration additional involved injury. triggers via pathway, leading syndrome.

Language: Английский

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Emerging roles of intratumor microbiota in cancer: tumorigenesis and management strategies

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 11, 2024

Language: Английский

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HSP27/IL-6 axis promotes OSCC chemoresistance, invasion and migration by orchestrating macrophages via a positive feedback loop

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: Jan. 28, 2025

Novel strategies to disrupt tumor progression have emerged from studying the interactions between cells and tumor-associated macrophages (TAMs). However, molecular mechanisms of TAMs underlying oral squamous cell carcinoma (OSCC) not been fully elucidated. This study explored mechanism HSP27/IL-6 axis in OSCC chemoresistance, invasion, migration. Here, we demonstrated higher expression HSP27 cells. Paracrine enhanced migration, EMT by inducing M2 polarization IL-6 secretion TAMs. established a positive feedback loop TAMs-derived orchestrated stemness chemoresistance through upregulating β-catenin CD44, via autocrine HSP27/TLR4 signaling. Collectively, facilitates migration orchestrating loop. We identify regulatory interaction crosstalk mediated axis. Targeting could be promising treatment strategy for patients, potentially controlling disease improving prognosis recurrence outcomes.

Language: Английский

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Langhans giant cells regulate cutaneous immune responses during mycobacterial infection through CXCL1/CXCL2 secretion

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 152, P. 114447 - 114447

Published: March 14, 2025

Language: Английский

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Intratumoral Fusobacterium nucleatum is associated with better cancer-specific survival in head and neck cancer patients

Journal of Oral Microbiology, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 1, 2025

The oral microbiome, particularly Fusobacterium nucleatum (Fn), has been implicated in head and neck cancers (HNC), influencing local immunity Human Papillomavirus (HPV) status. Here, we evaluated the presence of Fn its association with HPV infection, TERT promoter (TERTp) mutations, patient outcomes. We analyzed 94 formalin-fixed paraffin-embedded (FFPE) tumor tissues from HNC patients previously for TERTp mutations. DNA was detected using droplet digital PCR (ddPCR), status determined via p16 immunohistochemistry pre-treatment samples. Associations between presence, clinicopathological features, HPV, mutation were assessed. Tumors primarily originated oropharynx (70.2%) cavity (29.8%). Tobacco alcohol use reported 87.2% 79.8% cases, respectively. present 59.6% higher prevalence oropharyngeal (62.1%) than (53.6%) tumors. No significant associations found TERTp, or However, positivity showed significantly improved cancer-specific survival (61.5% vs. 39.1%, p = 0.013), similar to HPV-positive (72.7% 42.7%, 0.014). correlates longer survival, highlighting potential as a prognostic marker.

Language: Английский

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Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: April 9, 2025

Non-small cell lung cancer (NSCLC) represents the most common pathological type of cancer, and combination neoadjuvant immunotherapy with chemotherapy has emerged as first-line treatment for NSCLC. Nevertheless, efficacy this therapeutic approach remains variable. The present study aims to examine impact chemoimmunotherapy in NSCLC patients, a view identifying key molecules, critical subpopulations, communication patterns spatial distributions that potentially correlate sensitivity. A total 16 tissue samples were collected from cohort 12 patients subjected single-cell RNA transcriptome sequencing. Our data demonstrated distribution CD4 + Treg T cells mCAFs indicated an immunosuppressive tumor microenvironment, while accumulation Th17 iCAFs could act positive marker sensitivity chemoimmunotherapy. Furthermore, significant high level SELENOP-macrophages was observed tissues responders, strong co-localization between antigen-presenting associated fibroblasts (CAFs) boundaries identified, indicating cooperative roles these two types response combined therapy. Moreover, be accumulated tertiary lymphoid structures, which further suggested its role recruiting lymphocytes. analysis cell-cell communication, based on transcriptomics, suggests interactions SELENOP-macrophages, apCAFs, CD8 significantly enhanced responders. In addition, recruited Naïve, Helper Naïve through pathways such cholesterol, interleukin, chemokine HLA when responding unveils dynamic transcriptional changes microenvironment non-small

Language: Английский

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Multi-omics analysis reveals the interplay between intratumoral bacteria and glioma

mSystems, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Emerging evidence highlights the potential impact of intratumoral microbiota on cancer. However, microbial composition and function in glioma remains elusive. Consequently, our study aimed to investigate community tissues elucidate its role development. We parallelly performed profiling, transcriptome sequencing, metabolomics detection tumor adjacent normal brain obtained from 50 patients. employed immunohistochemistry, multicolor immunofluorescence, fluorescence

Language: Английский

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