Proteomic analysis of migrasomes derived from IL-6 amplifier-induced human breast cancer cells.

Integrative Proteomic Analysis Implicates Inhibition of Intracellular Protein Trafficking in Therapy-Induced Migrastasis in Prostate Cancer

KU2046-induced migrastasis appears to operate through spatial decoupling rather than structural degradation, providing a correlative framework to inhibit metastatic dissemination independent of direct cytotoxicity.

Novel Roles of Splice-Derived Tumor Mirtrons in the Regulation of Macrophage Dichotomy 2310054

Immunofluorescence imaging demonstrated that mirtrons carried by tumor-derived exosomes are taken up by human monocyte U937 cells and are predominantly localized to the cytoplasm, consistent with the behavior of conventional miRNAs.

Proteomic and Functional Comparison of Extracellular Vesicles from Wild-Type and Lyn-Deficient Stromal Cells.

BRD4 contributes to the cytokine-induced acquisition of an IL-13RA2-positive inflammatory fibroblast phenotype

Abstract Background and Aims Inflammatory bowel diseases (IBDs) are characterized by chronic intestinal inflammation, in which inflammatory fibroblasts contribute to epithelial damage and amplification of mucosal inflammation. However, the molecular mechanisms regulating their pathogenic activity remain incompletely understood. This study investigated the role of the epigenetic reader BRD4 in the differentiation and function of IL-13RA2-expressing inflammatory fibroblasts in IBD. Methods Single-cell RNA sequencing datasets from IBD patients and controls were analyzed to define BRD4 expression across stromal populations. Protein expression was validated by immunofluorescence and flow cytometry in intestinal tissues and primary fibroblasts. Primary fibroblasts from IBD patients were stimulated with interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-α) to induce an inflammatory phenotype, and BRD4 function was assessed using the BRD4-targeting PROTAC AT1. Cytokine and chemokine expression was evaluated by RNA sequencing, real-time polymerase chain reaction (PCR), and ELISA, while neutrophil chemotaxis assays assessed the functional effects of fibroblast-derived mediators. Results BRD4 was significantly upregulated in inflammatory fibroblasts from IBD patients compared with other stromal subsets and controls. Inflamed tissues showed enrichment of BRD4⁺ and IL-13RA2⁺ fibroblasts. In vitro, cytokine stimulation induced IL-13RA2 expression in the majority of fibroblasts, all of which co-expressed BRD4. BRD4 degradation significantly reduced the proportion of IL-13RA2⁺ fibroblasts. BRD4⁺ fibroblasts exhibited a pro-inflammatory transcriptional profile, including CCL2, CXCL1, CXCL2, IL-11, IL-24, IL-32, and CSF3. Degradation of BRD4 markedly decreased the expression of these mediators and reduced neutrophil migration. Conclusions BRD4 contributes to cytokine-induced inflammatory activation and pro-inflammatory functions of intestinal fibroblasts in IBD. Targeting BRD4 may represent a potential strategy to modulate stromal cell-driven inflammation.

Oncostatin M orchestrates collective epithelial migration via HIF1A activation.

Extracellular signals strongly influence cell behavior, yet the mechanisms by which specific ligands mediate changes in phenotype remain unclear. The cytokine Oncostatin M (OSM) regulates homeostasis, wound healing, inflammation, and cancer progression. We previously found that OSM induces collective cell migration (CCM), a process whereby cells move as cohesive units while retaining cell-cell contacts, in MCF10A mammary epithelial cells. Here, we investigated how OSM drives CCM by comparing its effects with those elicited by epidermal growth factor (EGF) and interferon gamma (IFNG), defining ligand-specific phenotypes and molecular networks. Integrative transcriptomic and proteomic analyses identified hypoxia-inducible factor-1 (HIF1A) and signal transducer and activator of transcription 3 (STAT3) as central regulators of OSM responses. Functional validation revealed that HIF1A drives transcriptional programs associated with hypoxia, metabolic reprogramming, and immune pathways. Complement signaling emerged as a downstream effector of HIF1A, and its inhibition disrupted OSM-induced clustering and CCM. These findings establish a mechanistic link between OSM signaling, HIF1A activation, and CCM, demonstrating how cytokine-driven transcriptional reprogramming coordinates epithelial cell migration. Analysis of public breast cancer data indicate that this pathway is active in human tumors and may contribute to tissue remodeling, repair, and metastasis.

Upregulation of macrophage UPP1 promotes lung adenocarcinoma metastasis through an mtROS-cGAS-NLRP3 inflammasome axis.

A macrophage-specific immunometabolic circuit in which UPP1-driven mitochondrial stress activates the mtROS-cGAS-NLRP3 axis, promoting IL-1β-dependent macrophage-tumor crosstalk and metastatic progression is identified.