Migrasome Marker Epidermal Growth Factor Domain-Specific O-GlcNAc Transferase: Pan-Cancer Angiogenesis Biomarker and the Potential Role of circ_0058189/miR-130a-3p/EOGT Axis in Hepatocellular Carcinoma Progression and Sorafenib Resistance

Biomedicines, Год журнала: 2025, Номер 13(4), С. 773 - 773

Опубликована: Март 22, 2025

Background: The EGF domain-specific O-GlcNAc transferase (EOGT), a migrasome marker, plays emerging roles in cancer biology through O-GlcNAcylation modifications, yet its pan-cancer functions and therapeutic implications remain underexplored. This study aimed to systematically characterize EOGT’s oncogenic mechanisms across malignancies, with particular focus on hepatocellular carcinoma (HCC) progression sorafenib resistance. Methods: Multi-omics analysis integrated TCGA/GTEx data from 33 types spatial/single-cell transcriptomics 10 HCC cohorts. Functional validation employed Huh7 cell models EOGT modulation, RNA sequencing, ceRNA network construction. Drug sensitivity leveraged GDSC/CTRP/PRISM databases, while immune microenvironment assessment utilized ESTIMATE/TIMER algorithms. Results: showed cancer-specific dysregulation, marked by significant upregulation correlating advanced stages poor survival. Pan-cancer revealed association genomic instability, tumor stemness, angiogenesis. Experimental demonstrated promotion of proliferation migration. A novel exosomal circ_0058189/miR-130a-3p/EOGT axis was identified, showing that circ_0058189 upregulated tissues, plasma samples exosomes sorafenib-resistant cells. Conclusion: establishes as angiogenesis biomarker, elucidating role resistance via circRNA-mediated regulation, providing mechanistic insights for targeted intervention strategies.

Язык: Английский

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The stromal microenvironment endows pancreatic neuroendocrine tumors with spatially specific invasive and metastatic phenotypes

Cancer Letters, Год журнала: 2024, Номер 588, С. 216769 - 216769

Опубликована: Март 2, 2024

Язык: Английский

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Integrative Chinese-Western medicine strategy to overcome docetaxel resistance in prostate cancer

Journal of Ethnopharmacology, Год журнала: 2024, Номер 331, С. 118265 - 118265

Опубликована: Апрель 25, 2024

Язык: Английский

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ITGB5 facilitates gastric cancer metastasis by promoting TGFBR2 endosomal recycling

Cancer Letters, Год журнала: 2024, Номер 592, С. 216953 - 216953

Опубликована: Май 9, 2024

Язык: Английский

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Bacteroidetes promotes esophageal squamous carcinoma invasion and metastasis through LPS-mediated TLR4/Myd88/NF-κB pathway and inflammatory changes

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 4, 2024

Abstract Gut microbiota plays a crucial role in gastrointestinal tumors. Additionally, gut microbes influence the progression of esophageal cancer. However, major bacterial genera that affect invasion and metastasis cancer remain unknown, underlying mechanisms unclear. Here, we investigated flora metabolites patients with squamous cell carcinoma found abundant Bacteroides increased secretion entry surface antigen lipopolysaccharide (LPS) into blood, causing inflammatory changes body. We confirmed these results mouse model 4NQO-induced situ further identified epithelial–mesenchymal transition (EMT) occurrence TLR4/Myd88/NF-κB pathway activation vitro experiments revealed LPS from fragile promoted proliferation, migration, invasion, induced EMT by activating pathway. These reveal are closely associated through higher response level signaling both common to inflammation tumors LPS, providing new biological target for prevention or treatment.

Язык: Английский

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Single-cell RNA sequencing to map tumor heterogeneity in gastric carcinogenesis paving roads to individualized therapy

Cancer Immunology Immunotherapy, Год журнала: 2024, Номер 73(11)

Опубликована: Сен. 13, 2024

Gastric cancer (GC) is a highly heterogeneous disease with complex tumor microenvironment (TME) that encompasses multiple cell types including cells, immune stromal and so on. Cancer-associated cells could remodel the TME influence progression of GC therapeutic response. Single-cell RNA sequencing (scRNA-seq), as an emerging technology, has provided unprecedented insights into complicated biological composition characteristics at molecular, cellular, immunological resolutions, offering new idea for studies. In this review, we discuss novel findings from scRNA-seq datasets revealing origin evolution GC, powerful tool investigating transcriptional dynamics intratumor heterogeneity (ITH) in GC. Meanwhile, demonstrate vital within TME, T B macrophages, play important role progression. Additionally, also overview how facilitates our understanding about effects on individualized therapy patients. Spatial transcriptomes (ST) have been designed to determine spatial distribution capture local intercellular communication networks, enabling further relationship between background particular its functions. summary, other single-cell technologies provide valuable perspective molecular pathological hold promise advancing basic research clinical practice

Язык: Английский

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Extracellular Vesicles in Breast Cancer: From Intercellular Communication to Therapeutic Opportunities

Pharmaceutics, Год журнала: 2024, Номер 16(5), С. 654 - 654

Опубликована: Май 14, 2024

Breast cancer, a multifaceted and heterogeneous disease, poses significant challenges in terms of understanding its intricate resistance mechanisms devising effective therapeutic strategies. This review provides comprehensive overview the landscape extracellular vesicles (EVs) context breast highlighting their diverse subtypes, biogenesis, roles intercellular communication within tumour microenvironment (TME). The discussion spans various aspects, from EVs stromal cells cancer to influence on angiogenesis, immune response, chemoresistance. impact EV production different culture systems, including two dimensional (2D), three (3D), organoid models, is explored. Furthermore, this delves into potential presenting emerging strategies such as engineered for gene delivery, nanoplatforms targeted chemotherapy, disrupting derived treatment approach. Understanding these complex interactions milieu crucial identifying developing new targets.

Язык: Английский

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Stabilization of TGF‐β Receptor 1 by a Receptor‐Associated Adaptor Dictates Feedback Activation of the TGF‐β Signaling Pathway to Maintain Liver Cancer Stemness and Drug Resistance

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Июль 9, 2024

Abstract Dysregulation of the transforming growth factor‐β (TGF‐β) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug‐resistant CSCs. Through a genome‐wide CRISPR activation screen utilizing stem‐like properties as readout, TGF‐β receptor‐associated binding protein 1 (TGFBRAP1) is identified TGF‐β‐inducible positive regulator that governs sensitivity tyrosine kinase inhibitors (TKIs) promotes liver stemness. By interacting with stabilizing receptor type (TGFBR1), TGFBRAP1 plays an important role in potentiating signaling. Mechanistically, competes E3 ubiquitin ligases Smurf1/2 for TGFΒR1, leading impaired poly‐ubiquitination proteasomal degradation. Moreover, hyperactive turn up‐regulates expression CSC‐like cells, thereby constituting previously uncharacterized mechanism amplify As such, correlated TGFΒR1 levels activity hepatocellular carcinoma (HCC) tissues, well overall survival disease recurrence multiple HCC cohorts. Therapeutically, blocking TGFBRAP1‐mediated stabilization TGFBR1 by selective alleviates Regorafenib resistance via reducing Collectively, targeting machinery may be actionable approach mitigate

Язык: Английский

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Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging

Опубликована: Авг. 5, 2024

The α-Klotho protein (hereafter Klotho) is an obligate coreceptor for fibroblast growth factor 23 (FGF23). It produced in the kidneys, brain and other sites. Klotho insufficiency causes hyperphosphatemia anomalies. Importantly, it associated with chronic pathologies (often age-related) that have inflammatory component. This includes atherosclerosis, diabetes Alzheimer’s disease. Its mode of action these diseases not well understood, but inhibits or regulates multiple major pathways. has a membrane form, soluble form (s-Klotho). Cytosolic postulated characterized. s-Klotho endocrine properties are incompletely elucidated. binds to FGF receptor 1c (FGFR1c) widely expressed (including endothelial cells). also attaches FGF23, FGF23/Klotho FGFRs. Thus, might be roaming FGF23 coreceptor, functions. Notably, (cell-bound soluble) counteracts inflammation, appears mitigate related aging (inflammaging). NF-κB NLRP3 inflammasome. inflammasome requires priming by NF-κB, produces active IL-1β, pores cell death (pyroptosis). In accord, countered inflammation injury induced toxins, damage-associated molecular patterns (DAMPs), cytokines, reactive oxygen species (ROS). blocks TGF-β Wnt ligands, which lessens fibrotic Low loss muscle mass (sarcopenia), as occurs diseases. counters inhibitory effects myostatin on muscle, reduces improves repair following injury. Inhibition factors may protective diabetic retinopathy age-related macular degeneration (AMD). review examines functions especially potential applications.

Язык: Английский

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Inhibition of EMT driver PTK6 enhances anti-tumor immune responses against triple-negative breast cancer

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

ABSTRACT The non-receptor tyrosine kinase PTK6 is expressed in 70% of triple negative breast cancers (TNBC) and an oncogenic driver epithelial-mesenchymal transition (EMT). EMT promotes metastasis immune evasion TNBC. Therefore, targeting drivers could reverse these properties lead to more favorable outcomes. Treatment TNBC tumors with a small molecule inhibitor (P21d) suppressed their growth vivo . Tumor inhibition by P21d dependent on induced response because: 1) observed immunocompetent, but not immunodeficient, mice; 2) increases tumor-infiltrating CD8 + T NK cells decreases immunosuppressive myeloid-derived suppressor cells; 3) tumor abrogated co-treatment or cell-depleting antibodies. These effects cytotoxic TILs are phenocopied the knockdown tumoral SNAIL, which supports as mechanism for enhanced anti-tumor response. RNA sequencing (RNA-seq) profiling P21d-treated also revealed changes consistent activation identified CXCL10 critical chemokine intratumorally that recruitment NK/CD8+ site, leading inhibition. Our study highlights novel microenvironmental functions important consequences new immunotherapeutic approaches

Язык: Английский

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