Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: June 10, 2021

Abstract To flourish, cancers greatly depend on their surrounding tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in TME are critical for cancer occurrence progression because of versatile roles extracellular matrix remodeling, maintenance stemness, blood vessel formation, modulation metabolism, immune response, promotion cell proliferation, migration, invasion, therapeutic resistance. CAFs highly heterogeneous stromal cells crosstalk with is mediated by a complex intricate signaling network consisting transforming growth factor-beta, phosphoinositide 3-kinase/AKT/mammalian target rapamycin, mitogen-activated protein kinase, Wnt, Janus kinase/signal transducers activators transcription, epidermal factor receptor, Hippo, nuclear kappa-light-chain-enhancer activated B cells, etc., pathways. These signals exhibit own special characteristics during the have potential to be targeted anticancer therapy. Therefore, comprehensive understanding these cascades interactions between necessary fully realize pivotal cancers. Herein, this review, we will summarize enormous amounts findings mediating its related targets or trials. Further, hypothesize three targeting strategies, including, namely, epithelial–mesenchymal common targets, sequential perturbation, crosstalk-directed paving way CAF-directed host cell-directed antitumor

Language: Английский

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Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 10, 2021

Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long (lncRNAs), and circular (circRNAs), are closely related variety biological functional aspects human health. When the exosomal ncRNAs undergo tissue-specific changes due diverse internal or external disorders, they can cause tissue dysfunction, aging, diseases. In this review, we comprehensively discuss underlying regulatory mechanisms exosomes in addition, explore current knowledge on roles miRNAs, lncRNAs, circRNAs health diseases, including cancers, metabolic neurodegenerative cardiovascular autoimmune infectious determine their potential implication biomarker identification therapeutic exploration.

Language: Английский

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Recent advances in exosome-mediated nucleic acid delivery for cancer therapy

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: June 14, 2022

Abstract Cancer is a leading public health problem worldwide. Its treatment remains daunting challenge, although significant progress has been made in existing treatments recent years. A large concern the poor therapeutic effect due to lack of specificity and low bioavailability. Gene therapy recently emerged as powerful tool for cancer therapy. However, delivery methods limit its effects. Exosomes, subset extracellular vesicles secreted by most cells, have characteristics good biocompatibility, toxicity immunogenicity, great designability. In past decades, carriers diagnostic markers, they caught extensive attention. This review introduced exosomes, focused on their applications DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering (siRNA), circular (circRNA) other nucleic acids. Meanwhile, application exosome-based clinical trials were presented discussed. Through systematic summarization analysis, advances current challenges exosome-mediated acid are introduced, which will provide theoretical basis development drugs. Graphical

Language: Английский

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Exosome-derived noncoding RNAs in gastric cancer: functions and clinical applications

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: July 30, 2021

Exosomes are a subpopulation of the tumour microenvironment (TME) that transmit various biological molecules to promote intercellular communication. derived from nearly all types cells and exist in body fluids. Noncoding RNAs (ncRNAs) among most abundant contents exosomes, some ncRNAs with functions specifically packaged into exosomes. Recent studies have revealed exosome-derived play crucial roles tumorigenesis, progression drug resistance gastric cancer (GC). In addition, regulating expression levels exosomal can or suppress GC progression. Moreover, membrane structures exosomes protect degradation by enzymes other chemical substances, significantly increasing stability ncRNAs. Specific hallmarks within be used for exosome identification, specific determine their origin. Therefore, suitable use as diagnostic prognostic biomarkers therapeutic targets. Regulating biogenesis may represent new way block eradicate GC. this review, we summarized origins characteristics analysed association between development.

Language: Английский

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Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy

Stem Cells, Journal Year: 2021, Volume and Issue: 39(4), P. 467 - 481

Published: Jan. 18, 2021

Abstract Degeneration of the cartilage endplate (CEP) induces intervertebral disc degeneration (IVDD). Nucleus pulposus cell (NPC) apoptosis is also an important exacerbating factor in IVDD, but cascade mechanism IVDD not clear. We investigated NPCs and when stimulated by normal stem (CESC)-derived exosomes (N-Exos) degenerated CESC-derived (D-Exos) vitro vivo. Tert-butyl hydroperoxide (TBHP) was used to induce inflammation CESCs. The bioinformatics differences between N-Exos D-Exos were analyzed using mass spectrometry, heat map, Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis. NPC examined TUNEL staining. involvement AKT autophagy signaling pathways inhibitor LY294002. Magnetic resonance imaging, Western blotting, immunofluorescence staining evaluate therapeutic effects rats with IVDD. TBHP effectively induced CEP rat. more conducive activation than D-Exos. apoptotic rate decreased obviously after treatment compared inhibited attenuated rat via pathways. These results are first findings confirm that delayed progression exosomes. on inhibition slowing effective due PI3K/AKT/autophagy pathway, which explained increase incidence CEP.

Language: Английский

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Therapeutic potential of RNA-enriched extracellular vesicles: The next generation in RNA delivery via biogenic nanoparticles

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(9), P. 2939 - 2949

Published: Feb. 27, 2024

Language: Английский

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Exosomes: compositions, biogenesis, and mechanisms in diabetic wound healing

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 5, 2024

Abstract Diabetic wounds are characterized by incomplete healing and delayed healing, resulting in a considerable global health care burden. Exosomes lipid bilayer structures secreted nearly all cells express characteristic conserved proteins parent cell-associated proteins. harbor diverse range of biologically active macromolecules small molecules that can act as messengers between different cells, triggering functional changes recipient thus endowing the ability to cure various diseases, including diabetic wounds. accelerate wound regulating cellular function, inhibiting oxidative stress damage, suppressing inflammatory response, promoting vascular regeneration, accelerating epithelial facilitating collagen remodeling, reducing scarring. from tissues or potentially possess functions varying levels promote healing. For example, mesenchymal stem cell-derived exosomes (MSC-exos) have favorable potential field due their superior stability, permeability, biocompatibility, immunomodulatory properties. Exosomes, which derived skin components, modulate inflammation regeneration key turn promotes Therefore, this review mainly emphasizes roles mechanisms sources, represented MSCs improving A deeper understanding therapeutic will yield promising candidates perspectives for management.

Language: Английский

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The role of microRNAs in the gastric cancer tumor microenvironment

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 20, 2024

Gastric cancer (GC) is one of the deadliest malignant tumors with unknown pathogenesis. Due to its treatment resistance, high recurrence rate, and lack reliable early detection techniques, a majority patients have poor prognosis. Therefore, identifying new tumor biomarkers therapeutic targets essential. This review aims provide fresh insights into enhancing prognosis GC by summarizing processes through which microRNAs (miRNAs) regulate microenvironment (TME) highlighting their critical role in TME. A comprehensive literature was conducted focusing on interactions among cells, extracellular matrix, blood vessels, cancer-associated fibroblasts, immune cells within The noncoding RNAs, known as miRNAs, modulating TME various signaling pathways, cytokines, growth factors, exosomes specifically examined. Tumor formation, metastasis, therapy are significantly influenced miRNAs progression these multiple exosomes. Dysregulation affects cellular such cell proliferation, differentiation, angiogenesis, contributing pathogenesis GC. play crucial regulation TME, influencing patient By understanding mechanisms control potential can be identified improve

Language: Английский

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Exosomal miRNAs: the tumor's trojan horse in selective metastasis

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 20, 2024

Organs of future metastasis are not passive receivers circulating tumor cells, but instead selectively and actively modified by the primary before metastatic spread has even occurred. Tumors orchestrate a pre-metastatic program conditioning distant organs to create microenvironments that foster survival proliferation cells their arrival, thereby establishing niches. Primary tumor-derived exosomes modulate these niches, generating permissive environment facilitates homing expansion cells. Moreover, microRNAs have emerged as key component exosomal cargo, serving only induce formation niches also prime sites for arrival colonization specific secondary populations. Against this backdrop, review endeavors elucidate impact on genesis individualized with view towards identifying novel means specifying cancer exploiting phenomenon immunotherapy.

Language: Английский

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Training and experimental validation a novel anoikis- and epithelial‒mesenchymal transition-related signature for evaluating prognosis and predicting immunotherapy efficacy in gastric cancer

Journal of Cancer, Journal Year: 2025, Volume and Issue: 16(4), P. 1078 - 1100

Published: Jan. 6, 2025

Anoikis resistance and improper activation of epithelial‒mesenchymal transition (EMT) are critical factors in tumor metastasis progression. Despite their interaction, the combined impact anoikis EMT on prognosis immunotherapy gastric cancer remains underexplored. In this study, we identified 354 anoikis- EMT-related genes (AERGs) through Venn analysis performed unsupervised clustering to classify patients into two molecular clusters: A B. Molecular cluster showed poor an immunosuppressive microenvironment, suggesting a "cold tumor" phenotype. Then, novel AERG-related prognostic model comprising CD24, CRYAB, MMP11, MUC4, PRKAA2, SERPINE1, SKP2, TP53 was constructed validated, accurately predicting 1-, 3-, 5-year survival rates patients. Multivariate revealed that risk score independent factor (hazard ratio = 1.651, 95% confidence interval 1.429-1.907, P<0.001). Further studies demonstrated that, compared high-risk group, low-risk group exhibited higher CD8+ T cell infiltration, mutational burden, immunophenoscores, lower immune dysfunction exclusion scores, indicating potential sensitivity immunotherapy. RT‒qPCR immunohistochemical staining validated expression levels model's markers. Overall, our shows promise for outcomes guiding selection tailored precise therapies

Language: Английский

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