Breast Cancer Research, Год журнала: 2025, Номер 27(1)
Опубликована: Май 5, 2025
Язык: Английский
Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)
Опубликована: Апрель 24, 2024
Abstract Tumors are highly complex and heterogenous ecosystems where malignant cells interact with healthy the surrounding extracellular matrix (ECM). Solid tumors contain large ECM deposits that can constitute up to 60% of tumor mass. This supports survival growth cancerous plays a critical role in response immune therapy. There is untapped potential targeting cell-ECM interactions improve existing therapy explore novel therapeutic strategies. The most abundant proteins collagen family. 28 different subtypes undergo several post-translational modifications (PTMs), which alter both their structure functionality. Here, we review current knowledge on composition consequences PTMs affecting receptor binding, cell migration stiffness. Furthermore, discuss how these alterations impact responses could be targeted treat cancer.
Язык: Английский
Процитировано
14
Biomaterials, Год журнала: 2025, Номер 321, С. 123340 - 123340
Опубликована: Апрель 12, 2025
Язык: Английский
Процитировано
1
Trends in Cell Biology, Год журнала: 2023, Номер 34(5), С. 406 - 415
Опубликована: Сен. 12, 2023
Язык: Английский
Процитировано
19
Drug Discovery Today, Год журнала: 2024, Номер 29(5), С. 103975 - 103975
Опубликована: Апрель 4, 2024
Язык: Английский
Процитировано
9
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Дек. 28, 2024
Abstract Cancer-associated fibroblasts (CAFs) exert multiple tumor-promoting functions and are key contributors to drug resistance. The mechanisms by which specific subsets of CAFs facilitate oxaliplatin resistance in colorectal cancer (CRC) have not been fully explored. This study found that THBS2 is positively associated with CAF activation, epithelial-mesenchymal transition (EMT), chemoresistance at the pan-cancer level. Together single-cell RNA sequencing spatial transcriptomics analyses, we identified specifically derived from CAFs, termed + could promote interacting malignant cells via collagen pathway CRC. Mechanistically, COL8A1 secreted directly interacts ITGB1 receptor on resistant cells, activating PI3K-AKT signaling promoting EMT, ultimately leading Moreover, elevated promotes EMT contributes CRC resistance, can be mitigated knockdown or AKT inhibitor. Collectively, these results highlight crucial role provide a rationale for novel strategy overcome
Язык: Английский
Процитировано
7
Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(1), С. e010029 - e010029
Опубликована: Янв. 1, 2025
To date, a growing body of evidence suggests that unfolded protein response (UPR) sensors play vital role in carcinogenesis. However, it remains unclear whether they are involved pancreatic ductal adenocarcinoma (PDAC) and how relate to clinical outcomes. This study aims investigate the biological function mechanism novel UPR sensor, CREB3L1 works PDAC further evaluate its application prospect. We tested signaling including Thapsigargin-treated cells. Subsequently, we defined expression analyzed with characteristics PDAC. Then, established gene-modified cells determine functions cell proliferation migration capacity. Besides, constructed subcutaneously orthotopically transplanted mice models verify their progrowing pulmonary metastasis prove proinvasion role. What's more, RNAseq, qPCR, Western blotting, immunohistochemistry multicolor flow cytometry experiments were used explore worked Lastly, correlation immunotherapy outcome immune signatures explored patients advanced who received PD-1 antibody therapy. first confirmed could be induced by endoplasmic reticulum stressor found aberrant activation was associated poorer overall survival indicating protumor new sensor. Functionally, contributing malignant progression growth multiple vitro vivo models. Mechanistically, upregulated COL3A1 promoted dense stroma formation for facilitating knocking down disrupted function. Furthermore, CREB3L1-induced TAM polarization toward an M2 phenotype reduced infiltration CD8+ T Clinically, correlated as well checkpoint blockade (ICB) treatment CREB3L1aberrant indicated efficacy worse prognosis than low which might empower decision. Collectively, this revealed facilitated progression, shaped exclude tumor microenvironment distinguished therapy ICB promising molecular target biomarker treatment.
Язык: Английский
Процитировано
1
Holistic Integrative Oncology, Год журнала: 2025, Номер 4(1)
Опубликована: Янв. 15, 2025
Abstract Purpose Uveal melanoma (UM) is the most common intraocular malignancy in adults. Previous studies have examined intra-tumoral heterogeneity. However, spatial distribution of tumor cells within microenvironment and its relationship with progression still remains largely unclear. Our study aimed to analyze correlation between cell patterns prognosis UM. Methods In this paper, we performed transcriptomics (ST) sequencing on two UM samples describe different cellular patterns. Gene Ontology (GO) Kyoto Encyclopedia Genes, Genomes (KEGG) functional enrichment analysis, protein–protein interaction (PPI) network were define biological function each cluster. Differentially expressed genes (DEGs) survival analysis based datasets from The Cancer Genome Atlas (TCGA) Expression Omnibus (GEO) database further confirmed clinical prognosis. Results We found distribution. focal a distinct ribosome synthesis rRNA pathway. contrast, subpopulation tented distribute diffusely was related fatty acids metabolism profile, presumably supporting growth by providing energy. scattered cluster associated malignant behaviors involved extensive interactions, including COLLAGEN. Moreover, pseudo-time showed that migration started basal region through differentiation. According TCGA GEO database, characteristically poor Conclusions drew ST maps for first time. These findings revealed functions pointed towards specific subpopulations higher invasiveness as potential therapeutic targets. Together, our displayed an overview transcriptome explored heterogeneity at level.
Язык: Английский
Процитировано
1
Advanced Science, Год журнала: 2025, Номер unknown
Опубликована: Янв. 17, 2025
Abstract A previous study classifies solid tumors based on collagen deposition and immune infiltration abundance, identifying a refractory subtype termed armored & cold tumors, characterized by elevated diminished infiltration. Beyond its impact infiltration, also influences tumor angiogenesis. This systematically analyzes the association between immuno‐collagenic subtypes angiogenesis across diverse cancer types. As result, exhibit highest angiogenic activity in lung adenocarcinoma (LUAD). Single‐cell spatial transcriptomics reveal close interactions co‐localization of fibroblasts endothelial cells. In vitro experiments demonstrate that stimulates cells to express vascular growth factor (VEGFA) directly enhances vessel formation cell proliferation through sex determining region Y box 18 (SOX18) upregulation. Collagen inhibition via multiple approaches effectively suppresses vivo. addition, display superior responsiveness anti‐angiogenic therapy advanced LUAD cohorts. Post‐immunotherapy resistance, transformation into emerges as potential biomarker for selecting therapy. summary, is shown drive various cancers, providing novel actionable framework refine therapeutic strategies combining chemotherapy with treatments.
Язык: Английский
Процитировано
1
Journal of Hepatology, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Fibrosis is a pathological condition characterized by excessive accumulation of extracellular matrix (ECM) components, particularly collagens, leading to tissue scarring and organ dysfunction. In fibrosis, an imbalance between collagen synthesis (fibrogenesis) degradation (fibrolysis) results in the deposition fibrillar collagens disrupting structural integrity ECM and, consequently, architecture. associated with wide range chronic diseases, including liver cirrhosis, kidney pulmonary autoimmune diseases. Recently, concept "hot" "cold" fibrosis has emerged, referring immune status within fibrotic tissues nature fibrogenic signaling. Hot active cell infiltration inflammation, while cold auto- paracrine myofibroblast activation, exclusion quiescence. This article aims explore relationship hot role various types their biologically fragments modulating system, how serological biomarkers can help understanding disease-relevant interactions mesenchymal cells tissues. Additionally, we draw lessons from immuno-oncology research solid tumors shed light on potential strategies for treatment highlight advantage having "hot environment" treat enhancing through modulation system.
Язык: Английский
Процитировано
1
Hepatology Communications, Год журнала: 2024, Номер 8(7)
Опубликована: Июль 1, 2024
HCC is globally recognized as a major health threat. Despite significant progress in the development of treatment strategies for liver cancer, recurrence, metastasis, and drug resistance remain key factors leading to poor prognosis majority cancer patients. Thus, there an urgent need develop effective biomarkers therapeutic targets HCC. Collagen, most abundant diverse protein tumor microenvironment, highly expressed various solid tumors plays crucial role initiation progression tumors. Recent studies have shown that abnormal expression collagen microenvironment closely related occurrence, development, invasion, resistance, making it potential target possible diagnostic prognostic biomarker This article provides comprehensive review structure, classification, origin collagen, well its clinical value, offering new insights into diagnosis, treatment, assessment cancer.
Язык: Английский
Процитировано
6