Outside influences: The impact of extracellular matrix mechanics on cell migration

Current topics in developmental biology/Current Topics in Developmental Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Structural glycobiology – from enzymes to organelles

Biochemical Society Transactions, Год журнала: 2025, Номер 53(1)

Опубликована: Янв. 31, 2025

Biological carbohydrate polymers represent some of the most complex molecules in life, enabling their participation a huge range physiological functions. The complexity biological carbohydrates arises from an extensive enzymatic repertoire involved construction, deconstruction and modification. Over past decades, structural studies processing enzymes have driven major insights into mechanisms, supporting associated applications across medicine biotechnology. Despite these successes, our understanding how multienzyme networks function to create polysaccharides is still limited. Emerging techniques such as super-resolution microscopy cryo-electron tomography are now investigation native systems at near molecular resolutions. Here, we review classical vitro processing, alongside recent situ glycosylation-related processes. While considerable technical challenges remain, integration mechanisms with true context promises transform regulation, shining light upon processes driving functional essential biomolecules.

Язык: Английский

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Thymidine kinase 1 indicates resistance to immune checkpoint plus tyrosine kinase inhibition in renal cell carcinoma

Cellular Oncology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Immune checkpoint plus tyrosine kinase inhibition (IO + TKI) has emerged as the first-line therapy in metastatic renal cell carcinoma (RCC), but no biomarker can predict its efficacy. Thymidine 1 (TK1) is closely associated with immune evasion tumors. Metastatic RCC patients treated by IO TKI were enrolled from two cohorts (ZS-MRCC, n = 45; Javelin-101, 726). High-risk localized also (ZS-HRRCC, 40). TK1 was assessed RNA-sequencing all cohorts, and contexture flow cytometry immunohistochemistry. Higher expression found resistant to (p 0.025). High-TK1 group showed poor progression-free survival (PFS) both ZS-MRCC cohort (P 0.008) Javelin-101 0.036). By multivariate Cox regression, high-TK1 determined an independent factor for PFS (hazard ratio (HR) 3.855, P 0.002). decreased granzyme B+ CD8+ T cells (ρ=-0.22, 0.18), increased PD1+ CD4+ (ρ 0.33, 0.04), PDL1+ macrophages 0.45, < 0.001), regulatory 0.35, 0.03). A novel random forest (RF) risk score built machine learning based on immunologic parameters. Combined surpassed sunitinib monotherapy low RF (HR 0.158, inferior high (HR, 2.195, 0.001). could be a potential indicator therapeutic resistance, under therapy. The may help stratify

Язык: Английский

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EDA Fibronectin Microarchitecture and YAP Translocation during Wound Closure

ACS Biomaterials Science & Engineering, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Fibronectin (Fn) is an extracellular matrix glycoprotein with mechanosensitive structure–function. Extra domain A (EDA) Fn, a Fn isoform, not present in adult tissue but required for repair. Curiously, EDA linked to both regenerative and fibrotic Given that mechanoregulates cell behavior, organization during wound closure might play role mediating these differing responses. One mechanism by which cells sense respond their microenvironment activating transcriptional coactivator, yes-associated protein (YAP). Interestingly, YAP activity only similarly Therefore, this study aims evaluate how, normal closure, modulate translocation culturing human dermal fibroblasts on polydimethylsiloxane substrates mimicking (soft: 18 kPa) (stiff: 146 wounded skin. On stiffer wounds, assembled aligned comprising thinner fibers, suggesting increased microenvironmental tension. To if binding the of was essential overall organization, were treated Irigenin, inhibits within Fn. Blocking adhesion led randomly organized matrices thicker reduced tension even closure. whether signaling plays CA3, suppresses dose-dependent manner. Treatment CA3 also potential connected reducing Next, assessed impact organization. migrating softer wounds activity, substrates, they decreased activity. When Irigenin or These results suggest there may be disrupted between could restored when reestablishing instead drive

Язык: Английский

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Integrative bioinformatics analysis of high-throughput sequencing and in vitro functional analysis leads to uncovering key hub genes in esophageal squamous cell carcinoma

Hereditas, Год журнала: 2025, Номер 162(1)

Опубликована: Март 14, 2025

Abstract Background Esophageal squamous cell carcinoma (ESCA) is a type of cancer that starts in the cells lining esophagus, tube connecting throat to stomach. It known for its aggressive nature and poor prognosis. Understanding key factors drive this crucial developing better diagnostic tools treatments. Methods Gene expression profiles ESCA were analyzed using Expression Omnibus (GEO) datasets (GSE23400, GSE29001, GSE92396, GSE1420) from GEO database. Differentially expressed genes (DEGs) identified limma package, protein-protein interaction (PPI) network was constructed STRING Hub based on degree method. Further validation performed through reverse transcription quantitative PCR (RT-qPCR), mutational copy number variation (CNV) analysis via cBioPortal database, promoter methylation OncoDB GSCA databases, survival analysis, immune infiltration functional assays, including knockdown genes. Results We four hub genes, COL3A1, COL4A1, COL5A2, CXCL8 play significant roles ESCA. These highly tissues lines, with levels significantly (p-value < 0.001) elevated compared normal controls. Receiver operating characteristic (ROC) curve revealed exceptional performance all area under (AUC) values 1.0, indicating perfect sensitivity specificity distinguishing Mutational COL3A1 altered 67% samples, primarily missense mutations, while COL5A2 exhibited alterations 50% splice site mutations. Additionally, gene amplification patterns observed further validating their oncogenic potential progression. A 0.05) hypomethylation detected these suggesting regulatory role expression. Functional assays demonstrated knocking down COL4A1 led decreased proliferation, colony formation, migration, critical tumor involved pathways related extracellular matrix system modulation. Conclusion are development progression, particularly remodeling matrix, modulating system, promoting metastasis. findings suggest could serve as biomarkers diagnosing targets future therapies. Future research should focus vivo clinical testing assess therapeutic targeting treatment.

Язык: Английский

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A Single-Step Protein Extraction for Lung Extracellular Matrix Proteomics Enabled by the Photocleavable Surfactant Azo and timsTOF Pro

Molecular & Cellular Proteomics, Год журнала: 2025, Номер unknown, С. 100950 - 100950

Опубликована: Март 1, 2025

Язык: Английский

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Proteolysis of Extracellular Matrix in Human Disease 2.0

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2700 - 2700

Опубликована: Март 17, 2025

Extracellular matrix (ECM) proteins not only migrate during development and function as a scaffold to which various cells attach but also are known be substrates of ECM-degrading proteases outside [...]

Язык: Английский

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Phosphoinositide signalling in cell motility and adhesion

Nature Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Unraveling the triad of immunotherapy, tumor microenvironment, and skeletal muscle biomechanics in oncology

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 2, 2025

The intricate interaction between skeletal muscle biomechanics, the tumor microenvironment, and immunotherapy constitutes a pivotal research focus oncology. This work provides comprehensive review of methodologies for evaluating including handheld dynamometry, advanced imaging techniques, electrical impedance myography, elastography, single-fiber experiments to assess quality performance. Furthermore, it elucidates mechanisms, applications, limitations various modalities, immune checkpoint inhibitors, adoptive cell therapy, cancer vaccines, combined chemoimmunotherapy, while examining their effects on function systemic responses. Key findings indicate that although is effective in augmenting antitumor immunity, frequently induces muscle-related adverse such as weakness, fatigue, or damage, primarily mediated by cytokine release activation. underscores significance niches within microenvironment influencing treatment outcomes proposes strategies optimize therapy through personalized regimens combinatorial approaches. highlights need further formation interactions muscle-tumor. Our crucial advancing efficacy immunotherapy, reducing effects, ultimately improving survival rates life patients with cancer.

Язык: Английский

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Molecular dynamics of the matrisome across sea anemone life history

Опубликована: Апрель 2, 2025

The evolutionary expansion of extracellular matrix (ECM) molecules has been crucial for the establishment cell adhesion and transition from unicellular to multicellular life. Members pre-bilaterian phylum cnidaria offer an exceptionally rich perspective into metazoan core adhesome its original function in developmental morphogenetic processes. Here, we present ensemble ECM proteins associated factors starlet sea anemone Nematostella vectensis based on silico prediction quantitative proteomic analysis decellularized mesoglea different life stages. integration matrisome with single transcriptome atlases reveals that Nematostella’s complex is predominantly produced by gastrodermal cells, confirming homology cnidarian inner layer bilaterian mesoderm. larva polyp characterized upregulation metalloproteases basement membrane components including all members unusually diversified SVEP1/Polydom family, suggesting massive epithelial remodeling. enrichment Wnt/PCP pathway during this process further indicates directed rearrangements as a key contributor polyp’s morphogenesis. Mesoglea maturation adult polyps involves wound response similar molecular patterns growth regeneration. Our study identifies conserved matrisomal networks coordinate transitions history.

Язык: Английский

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