Notch signaling pathway in cancer: from mechanistic insights to targeted therapies

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Май 27, 2024

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The receptor ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical signaling transduction. Accumulating evidence indicates that the pathway serves as both an oncogenic factor a tumor suppressor various cancer types. Dysregulation of this promotes epithelial-mesenchymal transition angiogenesis malignancies, closely linked proliferation, invasion, metastasis. Furthermore, contributes maintaining stem-like properties cells, thereby enhancing invasiveness. regulatory metabolic reprogramming microenvironment suggests pivotal involvement balancing suppressive effects. Moreover, implicated conferring chemoresistance cells. Therefore, comprehensive understanding these biological processes crucial developing innovative therapeutic strategies targeting signaling. This review focuses on research progress cancers, providing in-depth insights into potential mechanisms regulation occurrence progression cancer. Additionally, summarizes pharmaceutical clinical trials therapy, aiming offer new human malignancies.

Язык: Английский

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Cancer-associated fibroblasts: a versatile mediator in tumor progression, metastasis, and targeted therapy

Cancer and Metastasis Reviews, Год журнала: 2024, Номер 43(3), С. 1095 - 1116

Опубликована: Апрель 11, 2024

Abstract Tumor microenvironment (TME) has been demonstrated to play a significant role in tumor initiation, progression, and metastasis. Cancer-associated fibroblasts (CAFs) are the major component of TME exhibit heterogeneous properties their communication with cells. This heterogeneity CAFs can be attributed various origins, including quiescent fibroblasts, mesenchymal stem cells (MSCs), adipocytes, pericytes, endothelial cells, mesothelial Moreover, single-cell RNA sequencing identified diverse phenotypes CAFs, myofibroblastic (myCAFs) inflammatory (iCAFs) being most acknowledged, alongside newly discovered subtypes like antigen-presenting (apCAFs). Due these heterogeneities, exert multiple functions tumorigenesis, cancer stemness, angiogenesis, immunosuppression, metabolism, As result, targeted therapies aimed at TME, particularly focusing on rapidly developing, fueling promising future advanced tumor-targeted therapy.

Язык: Английский

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Metabolic reprogramming in tumor immune microenvironment: Impact on immune cell function and therapeutic implications

Cancer Letters, Год журнала: 2024, Номер 597, С. 217076 - 217076

Опубликована: Июнь 19, 2024

Understanding of the metabolic reprogramming has revolutionized our insights into tumor progression and potential treatment. This review concentrates on aberrant pathways in cancer cells within microenvironment (TME). Cancer differ from normal their processing glucose, amino acids, lipids order to adapt heightened biosynthetic energy needs. These shifts, which crucially alter lactic acid, acid lipid metabolism, affect not only cell proliferation but also TME dynamics. explores various immune TME. From a therapeutic standpoint, targeting these alterations represents novel treatment strategy. discusses approaches regulation metabolism different nutrients influencing enhance response. In summary, this summarizes its as target for innovative strategies, offering fresh perspectives

Язык: Английский

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HMGB1 mediates epithelial-mesenchymal transition and fibrosis in silicosis via RAGE/β-catenin signaling

Chemico-Biological Interactions, Год журнала: 2025, Номер unknown, С. 111385 - 111385

Опубликована: Янв. 1, 2025

Язык: Английский

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Emerging role of RNA acetylation modification ac4C in diseases: Current advances and future challenges

Biochemical Pharmacology, Год журнала: 2023, Номер 213, С. 115628 - 115628

Опубликована: Май 27, 2023

Язык: Английский

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c-MET pathway in human malignancies and its targeting by natural compounds for cancer therapy

Phytomedicine, Год журнала: 2024, Номер 128, С. 155379 - 155379

Опубликована: Янв. 18, 2024

Язык: Английский

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Reduced SMEK1 regulates trophoblast migration and invasion in fetal growth restriction

Placenta, Год журнала: 2025, Номер 161, С. 65 - 75

Опубликована: Фев. 5, 2025

Fetal growth restriction (FGR) is a significant pregnancy condition characterized by the fetus failing to attain its full genetic potential. FGR primarily ascribed defective placentation, owing impaired trophoblast cellular function. The objective of this research elucidate pathogenic functions suppressor Mek1 (SMEK1) in FGR. Western blot and Immunofluorescence were used detect expression localization SMEK1 placenta. We overexpressed knocked down using plasmid or siRNA special targeted it. EdU Assay, flow cytometry, blot, Wound healing migration Transwell insert assay influence on mechanism regulating JEG3 cells was predicted employing transcriptomics bioinformatics analysis, validated blot. downregulated placentas. aberrant associated with cell invasion, but not proliferation, apoptosis. Transcriptomic analysis blots indicate that knockdown inhibited PI3K/Akt/mTOR pathway. A inhibition observed epithelial-mesenchymal transition (EMT) process within group. activation pathway partially restored invasive ability due cells. reduction may contribute development hindering EMT through modulation signaling

Язык: Английский

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Pathogenetic development, diagnosis and clinical therapeutic approaches for liver metastasis from colorectal cancer (Review)

International Journal of Oncology, Год журнала: 2025, Номер 66(3)

Опубликована: Фев. 14, 2025

Colorectal cancer (CRC) is a prevalent malignancy and significant proportion of patients with CRC develop liver metastasis (CRLM), which major contributor to CRC‑related mortality. The present review aimed comprehensively examine the pathogenetic development diagnosis CRLM clinical therapeutic approaches for treatment this disease. molecular mechanisms underlying were discussed, including role tumour microenvironment epithelial‑mesenchymal transition. also highlighted importance early detection current challenges in predicting CRLM. Various strategies reviewed, surgical resection, chemotherapy immunotherapy, potential novel therapies, such as selective internal radiation therapy Traditional Chinese Medicine. Despite recent advancements options, remains challenge due complexity heterogeneity CRC. emphasized need multidisciplinary approach integration emerging therapies improve patient outcomes.

Язык: Английский

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The Role of Natural Flavonoids as Telomerase Inhibitors in Suppressing Cancer Growth

Pharmaceuticals, Год журнала: 2023, Номер 16(4), С. 605 - 605

Опубликована: Апрель 17, 2023

Cancer is a complex and multifaceted group of diseases characterized by the uncontrolled growth spread abnormal cells. While cancer can be challenging life-altering, advances in research development have led to identification new promising anti-cancer targets. Telomerase one such target that overexpressed almost all cells plays critical role maintaining telomere length, which essential for cell proliferation survival. Inhibiting telomerase activity lead shortening eventual death, thus presenting itself as potential therapy. Naturally occurring flavonoids are class compounds already been shown possess different biological properties, including property. They present various everyday food sources richly fruits, nuts, soybeans, vegetables, tea, wine, berries, name few. Thus, these could inhibit or deactivate expression mechanisms, include inhibiting hTERT, mRNA, protein, nuclear translocation, binding transcription factors hTERT promoters, even shortening. Numerous line studies vivo experiments supported this hypothesis, serve vital innovative therapeutic option cancer. In light, we aim elucidate target. Subsequently, illustrated how commonly found natural demonstrate their via inactivation types, proving naturally useful agents.

Язык: Английский

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Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Июнь 7, 2024

Abstract Metastasis remains the principal cause of cancer-related lethality despite advancements in cancer treatment. Dysfunctional epigenetic alterations are crucial metastatic cascade. Among these, super-enhancers (SEs), emerging as new regulators, consist large clusters regulatory elements that drive high-level expression genes essential for oncogenic process, upon which cells develop a profound dependency. These SE-driven oncogenes play an important role regulating various facets metastasis, including promotion tumor proliferation primary and distal organs, facilitating cellular migration invasion into vasculature, triggering epithelial-mesenchymal transition, enhancing stem cell-like properties, circumventing immune detection, adapting to heterogeneity niches. This heavy reliance on SE-mediated transcription delineates vulnerable target therapeutic intervention cells. In this article, we review current insights characteristics, identification methodologies, formation, activation mechanisms SEs. We also elaborate roles functions SEs context metastasis. Ultimately, discuss potential novel targets their implications clinical oncology, offering future directions innovative treatment strategies.

Язык: Английский

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