Impact of glycolysis enzymes and metabolites in regulating DNA damage repair in tumorigenesis and therapy

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 23, 2025

Initially, it was believed that glycolysis and DNA damage repair (DDR) were two distinct biological processes independently regulate tumor progression. The former metabolic reprogramming rapidly generates energy generous intermediate metabolites, supporting the synthetic metabolism proliferation of cells. While DDR plays a pivotal role in preserving genomic stability, thus resisting cellular senescence cell death under both physiological radio-chemotherapy conditions. Recently, an increasing number studies have shown closely correlation between these processes, then promoting For instance, lactic acid, product glycolysis, maintains acidic microenvironment not only fosters invasion but also facilitates by enhancing AKT activity. Here, we provide comprehensive overview enzymes metabolites involved along with primary methods for DDR. Meanwhile, this review explores existing knowledge regulating Moreover, considering significant roles development resistance, present discusses effective direct or indirect therapeutic strategies targeted to

Язык: Английский

---

Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment

Cancer Communications, Год журнала: 2024, Номер 44(9), С. 929 - 966

Опубликована: Июль 12, 2024

Abstract The intrinsic oncogenic mechanisms and properties of the tumor microenvironment (TME) have been extensively investigated. Primary features TME include metabolic reprogramming, hypoxia, chronic inflammation, immunosuppression. Previous studies suggest that senescence‐associated secretory phenotypes mediate intercellular information exchange play a role in dynamic evolution TME. Specifically, hypoxic adaptation, dysregulation, phenotypic shifts immune cells regulated by cellular senescence synergistically contribute to development an immunosuppressive thereby promoting progression events. This review provides comprehensive summary processes which regulates tumor‐adapted TME, with focus on complex underlying relationship between changes biological functions cells. available findings components collectively potential applications challenges targeted senescence‐based combination therapies clinical settings are further discussed within context advancing senescence‐related research.

Язык: Английский

---

Application of photosensitive microalgae in targeted tumor therapy

Advanced Drug Delivery Reviews, Год журнала: 2025, Номер unknown, С. 115519 - 115519

Опубликована: Фев. 1, 2025

Язык: Английский

---

Untangling the Role of MYC in Sarcomas and Its Potential as a Promising Therapeutic Target

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 1973 - 1973

Опубликована: Фев. 25, 2025

MYC plays a pivotal role in the biology of various sarcoma subtypes, acting as key regulator tumor growth, proliferation, and metabolic reprogramming. This oncogene is frequently dysregulated across different sarcomas, where its expression closely intertwined with molecular features unique to each subtype. interacts critical pathways such cell cycle regulation, apoptosis, angiogenesis, amplifying aggressiveness resistance standard therapies. Furthermore, influences microenvironment by modulating cell-extracellular matrix interactions immune evasion mechanisms, further complicating therapeutic management. Despite well-established centrality pathogenesis, targeting directly remains challenging due "undruggable" protein structure. However, emerging strategies, including indirect inhibition via epigenetic modulators, transcriptional machinery disruptors, pathway inhibitors, offer new hope for treatment. review underscores importance understanding intricate roles subtypes guide development effective targeted Given MYC's central tumorigenesis progression, innovative approaches aiming at could transform landscape patients, providing much-needed avenue overcome improve clinical outcomes.

Язык: Английский

---

NK cells: shielding senescence homeostasis in the decidua during early pregnancy

Seminars in Immunopathology, Год журнала: 2025, Номер 47(1)

Опубликована: Март 11, 2025

Язык: Английский

---

Assessing male reproductive toxicity of environmental pollutant di-ethylhexyl phthalate with network toxicology and molecular docking strategy

Reproductive Toxicology, Год журнала: 2024, Номер 130, С. 108749 - 108749

Опубликована: Ноя. 17, 2024

Язык: Английский

---

Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcoma

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 22, 2025

Osteosarcoma is the most common malignant bone tumor in children and adolescents, characterized by high disability mortality rates. Over past three decades, therapeutic outcomes have plateaued, underscoring critical need for innovative targets. Solute carrier (SLC) family transporters been implicated progression of a variety tumors, however, their specific role osteosarcoma remains poorly understood. The single-cell sequencing data from GSE152048 GSE162454, along with RNA-seq TARGET GSE21257 cohorts, were utilized analysis this study. LASSO regression was conducted to identify prognostic genes construct an SLC-related signature. Survival ROC evaluated validity ESTIMATE CIBERSORT Packages assess immune infiltration status. Pseudotime CellChat analyses performed investigate relationship between SLC7A1, phenotypes, microenvironment. CCK8 assays, EdU staining, colony formation Transwell co-culture systems used effects SLC7A1 on cell proliferation, metastasis, macrophage polarization. Finally, virtual docking identified potential drugs targeting SLC7A1. SLCs displayed distinct expression patterns across various types within microenvironment, myeloid cells exhibiting preference amino acid uptake. A model comprising nine constructed via regression, showing highest hazard ratio. Multiple analytical algorithms indicated that associated checkpoint gene expression. Single-cell predominantly expressed correlated characteristics. also regulate interactions macrophages, as well modulate function through multiple pathways. In vitro assays survival demonstrated inhibition suppressed phenotype cells, correlating poor prognosis. Co-culture models confirmed involvement screening CETSA Cepharanthine inhibitors signatures can be evaluation osteosarcoma. Pharmacological may feasible approach

Язык: Английский

---

Comprehensive analysis of senescence-related genes identifies prognostic clusters with distinct characteristics in glioma

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 19, 2025

Cellular senescence, defined as a state of permanent arrest in cell growth, is regarded crucial tumor suppression mechanism. However, accumulating scientific evidence suggests that senescent cells play detrimental role the progression cancer. Unfortunately, current lack reliable markers specifically reflect level senescence cancer greatly hinders our in-depth understanding this important biological foundation. Therefore, search for more specific and to reveal particularly urgent important. To uncover gliomas, we collected senescence-related genes integrated analysis. Consensus clustering was used subtype gliomas based on gene set, identified two robust prognostic clusters with distinct survival outcomes, multi-omics landscapes, immune characteristics, differential drug responses. Multiple external datasets were validate stability subtypes. Various computational experimental methods, including WGCNA (Weighted Gene Co-expression Network Analysis), ssGSEA (single-sample Set Enrichment machine learning algorithms (lasso regression, support vector machines, random forests), employed We found CEBPB LMNA are associated poor prognosis may mediate immunosuppression proliferation. Drug prediction indicated dasatinib potential therapeutic agent. Our findings provide insights into set patient stratification precision medicine.

Язык: Английский

---

Targeting tumor angiogenesis and metabolism: a new perspective in pediatric thoracic tumor therapy

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Март 27, 2025

Pediatric thoracic solid tumors encompass mediastinal tumors, chest wall and lung tumors. The pathogenesis is complex, the clinical presentation diverse, presenting numerous challenges in diagnosis treatment, which severely threaten life health of affected children. Angiogenesis provides nutritional oxygen support for tumor growth metastasis, while metabolic reprogramming meets unique energy material demands tumor. Both processes play key roles pediatric development. Therefore, targeting vasculature could be an important therapeutic strategy, exploring molecular mechanisms may provide a theoretical foundation targeted treatment. This review summarizes relevant experimental research on angiogenesis analyzes limitations current research, proposes solutions recommendations. Through this review, we aim to comprehensive information about clinicians researchers, promoting personalized ultimately improve survival rates quality

Язык: Английский

---

A Senescence-Associated Gene Signature for Prognostic Prediction and Therapeutic Targeting in Adrenocortical Carcinoma

Biomedicines, Год журнала: 2025, Номер 13(4), С. 894 - 894

Опубликована: Апрель 8, 2025

Background/Objectives: Cellular senescence plays a critical role in tumorigenesis, immune cell infiltration, and treatment response. Adrenocortical carcinoma (ACC) is malignant tumor that lacks effective therapies. This study aimed to construct validate senescence-related gene signature as an independent prognostic predictor for ACC explore its impact on the microenvironment, immunotherapy, chemotherapy Methods: Data were collected from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) database. Using Kaplan–Meier survival analysis, LASSO penalized Cox regression multivariable regression, we identified model with four genes (HJURP, CDK1, FOXM1, CHEK1). model’s value was validated through risk score curves, receiver operating characteristic (ROC) curves. Tumor mutation burden assessed maftools, microenvironment analyzed using CIBERSORT ESTIMATE. Immune chemotherapeutic responses Dysfunction Exclusion (TIDE) OncoPredict. Results: derived our showed strong association overall (OS) patients (p < 0.001, HR = 2.478). Higher scores correlated more advanced stages greater frequency of somatic mutations. Differentially expressed (DEGs) downregulated high-risk group significantly enriched immune-related pathways. Furthermore, predicted have reduced sensitivity immunotherapy 0.02). Bioinformatics analysis potential agents, including BI-2536 MIM1, options patients. Conclusions: Our findings indicate this may serve valuable tool predicting patients, those receiving immunotherapy.

Язык: Английский

---