Metabolic Profiling of Breast Cancer Cell Lines: Unique and Shared Metabolites

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 969 - 969

Published: Jan. 24, 2025

Breast Cancer (BrCa) exhibits a high phenotypic heterogeneity, leading to the emergence of aggressive clones and development drug resistance. Considering BrCa heterogeneity that metabolic reprogramming is cancer hallmark, we selected seven cell lines with diverse subtypes provide their comprehensive metabolome characterization: five commonly used (SK-Br-3, T-47D, MCF-7, MDA-MB-436, MDA-MB-231), two patient-derived xenografts (Hbcx39 Hbcx9). We characterized endometabolomes using 1H-NMR spectroscopy. found distinct metabolite profiles, certain metabolites being common but differentially accumulated across lines. High levels glycine, lactate, glutamate, formate, known promote invasion metastasis, were detected in all cells. In our experiment setting identified unique specific lines: xanthine 2-oxoglutarate SK-Br-3, 2-oxobutyrate cystathionine glucose-1-phosphate NAD+ isocitrate MDA-MB-231, NADP+ Hbcx9. The enriched enabled us identify pathways modulated cell-line-specific manner, which may represent potential candidate targets for therapeutic intervention. believe this study contribute functional characterization cells assist selecting appropriate drug-response studies.

Language: Английский

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The CD64/CD28/CD3ζ chimeric receptor reprograms T-cell metabolism and promotes T-cell persistence and immune functions while triggering antibody-independent and antibody-dependent cytotoxicity

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: Feb. 17, 2025

Recent studies have shown that CD32/CD8a/CD28/CD3ζ chimeric receptor cells directly kill breast cancer cells, suggesting the existence of cell surface myeloid FcγR alternative ligands (ALs). Here, we investigated metabolism, ALs, cytotoxicity, and immunoregulatory functions CD64/CD28/CD3ζ in colorectal (CRC) squamous carcinoma head neck. The -SFG retroviral vector was used to produce viruses for T-cell transduction. expansion differentiation were monitored via flow cytometry. Gene expression assessed by RNA-seq. Bioenergetics documented on a Seahorse extracellular flux analyzer. polarization identified confocal microscopy. Cytotoxicity determined MTT assay bioluminescent imaging, Tridimensional antitumor activity T achieved utilizing HCT116-GFP 3D spheroids IncuCyte S3 Live-Cell Analysis system. intraperitoneal distribution NIR-CD64/CD28/CD3ζ NIR-nontransduced CB17-SCID mice bearing subcutaneous FaDu Luc + fluorescent imaging. IFNγ ELISA. Compared CD16/CD8a/CD28/CD3ζ non-transduced exhibited highest levels persistence capacity. A total 235 genes linked division 52 related glycolysis overexpressed. glycolytic phenotype confirmed functional vitro accompanied preferential effector memory differentiation. Interestingly, oxamic acid found inhibit CD64-CR proliferation, indicating involvement lactate. Upon conjugation with CRC polarize at immunological synapses, leading death. SCCHN combination anti-B7-H3 mAb (376.96) or anti-EGFR mAb, these trigger antibody-dependent cellular cytotoxicity (ADCC) under 2D conditions. 376.96 combined had anti-SCCHN vivo. In addition, they induce upregulation PD-L1 HLA-DR IFNγ. positive anti-PD-L1 killed ADCC, which enhanced direct cytotoxicity. These findings indicate is involved proliferation/expansion. mediate long-lasting HLA-independent ADCC cells. could significantly impact rational design personalized treat identification novel ALs healthy

Language: Английский

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Plant-derived terpenoids modulating cancer cell metabolism and cross-linked signaling pathways: an updated reviews

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Language: Английский

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Interplay of Metastasis, Cancer Stem Cells, and Energy Metabolism in Cancer Progression

Current Tissue Microenvironment Reports, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

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HOTAIR Participation in Glycolysis and Glutaminolysis Through Lactate and Glutamate Production in Colorectal Cancer

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 388 - 388

Published: March 6, 2025

Metabolic reprogramming plays a crucial role in cancer biology and the mechanisms underlying its regulation represent promising study area. In this regard, discovery of non-coding RNAs opened new regulatory landscape, which is early stages investigation. Using differential expression model HOTAIR, we evaluated level metabolic enzymes, as well metabolites produced by glycolysis glutaminolysis. Our results demonstrated effect HOTAIR on glutaminolysis enzymes colorectal cells. Specifically, through overexpression inhibition determined influence PFKFB4, PGK1, LDHA, SLC1A5, GLUD1, GOT1, had direct impact lactate glutamate production. These findings indicate that significant producing “oncometabolites” essential to maintaining bioenergetics biomass necessary for tumor cell survival regulating

Language: Английский

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Large-scale CRISPRi screens link metabolic stress to glioblastoma chemoresistance

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 6, 2025

Glioblastoma (GBM) patients frequently develop resistance to temozolomide (TMZ), the standard chemotherapy. While targeting cancer metabolism shows promise, relationship between metabolic perturbation and drug remains poorly understood. We performed high-throughput CRISPR interference screens in GBM cells identify genes modulating TMZ sensitivity. Findings were validated using multiple cell lines, patient-derived glioma stem cells, clinical data. Molecular mechanisms investigated through transcriptome analysis, profiling, functional assays. identified phosphoglycerate kinase 1 (PGK1) as a key determinant of Paradoxically, while PGK1 inhibition suppressed tumor growth, it enhanced by inducing stress. This activated AMPK HIF-1α pathways, leading DNA damage repair 53BP1. expression levels correlated with sensitivity across models patient samples. Our study reveals an unexpected link stress chemoresistance, demonstrating how adaptation can promote therapeutic resistance. These findings caution against single-agent suggest potential biomarker for response GBM.

Language: Английский

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Advancing Bladder Cancer Biomarker Discovery: Integrating Mass Spectrometry and Molecular Imaging

Onco, Journal Year: 2025, Volume and Issue: 5(2), P. 13 - 13

Published: March 24, 2025

Bladder cancer, a highly heterogeneous disease, necessitates precise diagnostic and therapeutic strategies to enhance patient outcomes. Metabolomics, through comprehensive small-molecule analysis, provides valuable insights into cancer-associated metabolic alterations at the cellular, tissue, systemic levels. Concurrently, molecular imaging modalities like PET, MRI, CT enable non-invasive, real-time visualization of tumor biology, facilitating spatial functional assessment biomarkers. Key findings highlight identification metabolomic profiles correlated with cancer progression, recurrence, treatment responses across serum, urine, tissue samples. Advanced analytical platforms, such as LC-MS NMR, uncover distinct signatures pathway in glycolysis, amino acid metabolism, lipid biosynthesis. Molecular further enhances staging accuracy monitoring by visualizing activity receptor expression. The integration these technologies addresses limitations invasive methods paves way for precision oncology. Future advancements should focus on multi-omics integration, AI-driven large-scale clinical validation ensure broad accessibility transformative impacts bladder management.

Language: Английский

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Targeting the Hippo Pathway in Breast Cancer: A Proteomic Analysis of Yes-Associated Protein Inhibition

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 3943 - 3943

Published: April 22, 2025

The dysregulation of the Hippo signaling pathway leads to aberrant activation oncogenic YAP and TAZ, driving tumor progression. In breast cancer, this disruption promotes proliferation metastasis. This study investigates effects CA3, a selective inhibitor, on proteome triple-negative cancer MDA-MB-231 luminal-A-like MCF7 cells. Proteomic changes were analyzed via nano-LC-MS/MS, while cytotoxicity, apoptosis, autophagy assessed through WST-1 assays, flow cytometry, Western blot analyses. Bioinformatics tools employed identify enriched pathways. cells exhibited an increased expression DNA repair proteins (p < 0.05), indicating compensatory response maintain genomic stability. contrast, showed downregulation factors 0.005). Additionally, metabolic reprogramming was apparent in 0.001). Apoptosis assays revealed rise cell death, cycle analysis indicated pronounced G1-phase arrest 0.01). Moreover, autophagic suppression particularly evident study, for first time, provides evidence that subtypes exhibit distinct dependencies YAP-driven pathways, revealing potential therapeutic vulnerabilities. Targeting alongside or combining inhibition with blockade luminal holds significant enhance treatment efficacy.

Language: Английский

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Mitochondrial ribosomal proteins: potential targets for cancer prognosis and therapy

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

Published: April 30, 2025

Mitochondrial ribosomal proteins (MRPs) are essential components of mitochondrial ribosomes, responsible for translating encoded by DNA and maintaining energy metabolism function. Emerging evidence suggests that MRPs exhibit significant expression changes in multiple cancer types, profoundly affecting tumor biology through modulating oxidative stress levels, inducing metabolic reprogramming, disrupting cell cycle regulation, inhibiting apoptosis, promoting mitophagy, remodeling the microenvironment. Specifically, have been implicated proliferation, migration, invasion, highlighting their potential as therapeutic targets. This review summarizes multifaceted roles cancer, focusing on impact microenvironment prognostic biomarkers We also explore implications precision oncology, particularly patient stratification design targeted therapies, offering new insights research directions precise prevention treatment cancer.

Language: Английский

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Exploring the Multifunctional Role of Alpha-Fetoprotein in Cancer Progression: Implications for Targeted Therapy in Hepatocellular Carcinoma and Beyond

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4863 - 4863

Published: May 19, 2025

Alpha-fetoprotein (AFP) is a well-known biomarker for liver cancer, and its clinical utility widely recognized. Recent studies have revealed that AFP plays multifaceted role in various malignant tumors, including cancer. This suggests not merely but also contributes significantly to the complex process of tumor formation, emphasizing importance targeting therapeutic approaches. Consequently, innovative research development are essential overcome current limitations AFP-targeted therapies, enhance treatment efficacy, minimize side effects. review explores cancer progression, highlights biological functions related pathways, discusses implications therapies. Ongoing on will contribute our understanding mechanisms aid developing effective safe treatments. Ultimately, advancements approaches expected play crucial future management.

Language: Английский

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