The RANK–RANKL–OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer

Medicina, Journal Year: 2023, Volume and Issue: 59(10), P. 1752 - 1752

Published: Sept. 30, 2023

The RANK-RANKL-OPG system is a complex signaling pathway that plays critical role in bone metabolism, mammary epithelial cell development, immune function, and cancer. RANKL ligand binds to RANK, receptor expressed on osteoclasts, dendritic cells, T other cells. promotes osteoclast differentiation activation, which leads resorption. OPG decoy inhibits its signaling. In cancer expression often increased, can lead increased resorption the development of metastases. RANKL-neutralizing antibodies, such as denosumab, have been shown be effective treatment skeletal-related events, including osteoporosis or metastases, This review will provide comprehensive overview functions cancer, together with potential therapeutic implications RANK-RANKL for management.

Language: Английский

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Enhancing therapeutic efficacy: sustained delivery of 5-fluorouracil (5-FU) via thiolated chitosan nanoparticles targeting CD44 in triple-negative breast cancer

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 19, 2024

Our current study reports the successful synthesis of thiolated chitosan-based nanoparticles for targeted drug delivery 5-Fluorouracil. This process was achieved through ionic gelation technique, aiming to improve efficacy chemotherapeutic moiety by modifying surface (NPs) with a ligand. We coated these NPs hyaluronic acid (HA) actively target CD44 receptor, which is frequently overexpressed in various solid malignancies, including breast cancer. XRD, FTIR, SEM, and TEM were used physicochemical analysis NPs. These 5-Fluorouracil (5-FU) loaded evaluated on MDA-MB-231 (a triple-negative cell line) MCF-10A (normal epithelial cells) determine their vitro efficacy. The developed 5-FU-loaded exhibited particle size within favorable range (< 300 nm). positive zeta potential facilitated uptake negatively charged cancer cells. Moreover, they demonstrated robust stability high encapsulation efficiency. significant cytotoxicity compared crude (p < 0.05) displayed promising release pattern consistent basic diffusion model. traits pharmacokinetic profile, efficacy, ability precisely nanoparticles, offering potentially anticancer treatment However, additional vivo assessments formulations are obligatory confirm findings.

Language: Английский

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The Role of Osteoprotegerin in Breast Cancer: Genetic Variations, Tumorigenic Pathways, and Therapeutic Potential

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 337 - 337

Published: Jan. 21, 2025

Introduction: Osteoprotegerin (OPG), encoded by the TNFRSF11B gene, is linked to development of breast cancer via several pathways, including interactions with receptor activator nuclear factor-κB (RANK) ligands, apoptosis-inducing proteins like TRAIL, and genetic variations such as single nucleotide polymorphisms (SNPs), directly altering gene expression. This review aims investigate role OPG expression in cancer. Methods: A comprehensive literature search was conducted using PubMed Medline, Google Scholar, ScienceDirect. Only full-text English publications from inception September 2024 were included. Results: Studies have demonstrated that certain SNPs specifically rs3102735 rs2073618, are a higher risk development. Additionally, OPG’s function TRAIL decoy may inhibit death cells. Furthermore, serum its BRCA mutations being investigated for their potential influence on progression. found promotes tumorigenesis enhancing cell proliferation, angiogenesis, aneuploidy normal mammary epithelial Moreover, mediates tumor-promoting effects interleukin-1 beta serve biomarker risk, particularly BRCA1 mutation carriers, through dysregulated RANK signaling. Lastly, use recombinant mouse models has been exert anti-tumor effects. Conclusions: In this review, examined. multifaceted exerts TNF-related ligand (TRAIL), modulation pro-tumorigenic microenvironment survival, metastasis. dual tumor suppressor promoter serves possible therapeutic target enhance apoptosis, limit bone metastasis, modulate microenvironment. Whilst much now known, further studies necessary fully delineate OPG.

Language: Английский

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Long Intergenic Non-Coding RNAs and BRCA1 in Breast Cancer Pathogenesis: Neighboring Companions or Nemeses?

Non-Coding RNA, Journal Year: 2025, Volume and Issue: 11(1), P. 9 - 9

Published: Jan. 29, 2025

Breast cancer is one of the leading causes mortality among women, primarily due to its complex molecular landscape and heterogeneous nature. The tendency breast patients develop metastases poses significant challenges in clinical management. Notably, mutations gene 1 (BRCA1) significantly elevate risk. current research endeavors employ diverse approaches, including RNA, DNA, protein studies, explore avenues for early diagnosis treatment cancer. Recent attention has shifted towards long non-coding RNAs (lncRNAs) as promising diagnostic, prognostic, therapeutic targets multifaceted progression Among these, intergenic (lincRNAs), a specific class lncRNAs, play critical roles regulating various aspects tumorigenesis, cell proliferation, apoptosis, epigenetic modulation, tumor invasion, metastasis. Their distinctive expression patterns cellular tissue contexts underscore their importance development progression. Harnessing lincRNAs’ sensitivity precision therapeutic, prognostic markers holds promise management However, potential lincRNAs remains relatively underexplored, particularly context BRCA1-mutated other clinicopathological parameters such receptor status patient survival. Consequently, there an urgent need comprehensive investigations into novel diagnostic biomarkers. This review examines associated with BRCA1 cancer, highlighting future applications.

Language: Английский

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Signaling pathway dysregulation in breast cancer

Oncotarget, Journal Year: 2025, Volume and Issue: 16(1), P. 168 - 201

Published: March 13, 2025

// Dinara Ryspayeva 1 , 2 3 4 Attila A. Seyhan 5 William J. MacDonald Connor Purcell Tyler Roady Maryam Ghandali Nataliia Verovkina Wafik S. El-Deiry 7 Martin Taylor 6 and Stephanie L. Graff Laboratory of Translational Oncology Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, RI 02903, USA Department Pathology Medicine, Joint Program in Biology, Lifespan Health System Legorreta Center at Pathobiology Graduate Program, on the Biology Aging, Hematology/Oncology Division, Correspondence to: Ryspayeva, email: [email protected] Keywords: breast cancer; oncogenic pathways; signal dysregulation therapeutic approaches; clinical trials Received: December 20, 2024 Accepted: March 03, 2025 Published: 13, Copyright: © et al. This is an open access article distributed under terms Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, reproduction any medium, provided original author source are credited. ABSTRACT provides a comprehensive analysis signaling pathways implicated cancer (BC), most prevalent malignancy among women leading cause cancer-related mortality globally. Special emphasis placed structural dynamics protein complexes that integral to regulation these cascades. Dysregulation cellular fundamental aspect BC pathophysiology, with both upstream downstream cascade activation contributing process aberrations not only drive tumor growth, but also contribute resistance against current treatments. The review explores alterations within across different subtypes highlights potential strategies targeting pathways. Additionally, influence specific mutations decision-making examined, underscoring their relevance particular subtypes. discusses approved modalities ongoing disrupted However, further investigation necessary fully elucidate underlying mechanisms optimize personalized treatment approaches.

Language: Английский

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Identification of BRCA1 Gene Mutation Variants in Clinical Samples without a Labeling Step─A Comparison of the Functionality and Sensitivity of SPR and SERS Sensors

The Journal of Physical Chemistry C, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Language: Английский

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Correlations of Imaging and Therapy in Breast Cancer Based on Molecular Patterns: An Important Issue in the Diagnosis of Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8506 - 8506

Published: Aug. 4, 2024

Breast cancer is a global health issue affecting countries worldwide, imposing significant economic burden due to expensive treatments and medical procedures, given the increasing incidence. In this review, our focus on exploring distinct imaging features of known molecular subtypes breast cancer, underlining correlations observed in clinical practice reported recent studies. The investigations used for assessment include screening modalities such as mammography ultrasonography, well more complex like MRI, which offers high sensitivity loco-regional evaluation, PET, determines tumor metabolic activity using radioactive tracers. purpose review provide better understanding revision differences exhibited by histopathological types cancer.

Language: Английский

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Targeting GPX4-mediated ferroptosis protection sensitizes BRCA1-deficient cancer cells to PARP inhibitors

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103350 - 103350

Published: Sept. 11, 2024

Language: Английский

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Toxoplasma gondii suppresses proliferation and migration of breast cancer cells by regulating their transcriptome

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 23, 2024

Abstract Background Breast cancer is the most common in women worldwide. Toxoplasma gondii ( T. ) has shown anticancer activity breast mouse models, and exerted beneficial effect on survival of patients, but mechanism was unclear. Methods The tachyzoites (RH ME49 strains) human cells (MCF-7 MDA-MB-231 cells) proliferation migration assessed using cell growth curve wound healing assays. Dual RNA-seq performed for gondii- infected non-infected to determine differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia Genes Genomes (KEGG), Protein–Protein Interaction Networks analysis (PPI) were explore related signaling pathway hub genes. Hub validated Kaplan–Meier plotter database, Pathogen Host (PHI-base) database. results verified by qRT-PCR. Results decreased expression Ki67 increased E-cadherin , resulting suppressing cells. inhibitory showed a significant dose–response relationship. Compared with control group, 2321 transcriptionally regulated MCF-7 while 169 Among these genes, 698 67 publicly available GO KEGG analyses suggested that several pathways involved function such as ribosome, interleukin-17 signaling, coronavirus disease pathway, pathway. BRCA1, MYC IL-6 identified top three infected-breast based connectivity PPI analysis. In addition, after interacting cells, ROP16 ROP18 increased, crt, TgIST, GRA15, GRA24 MIC13 decreased. Conclusions regulates altering which can inhibit tumor migration, hinting at potential therapeutic strategy.

Language: Английский

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E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease

Biochemical Journal, Journal Year: 2024, Volume and Issue: 481(14), P. 923 - 944

Published: July 10, 2024

Maintenance of genome stability is paramount importance for the survival an organism. However, genomic integrity constantly being challenged by various endogenous and exogenous processes that damage DNA. Therefore, cells are heavily reliant on DNA repair pathways have evolved to deal with every type genotoxic insult threatens compromise stability. Notably, inherited mutations in genes encoding proteins involved these protective trigger onset disease driven chromosome instability e.g. neurodevelopmental abnormalities, neurodegeneration, premature ageing, immunodeficiency cancer development. The ability regulate recruitment specific sites extremely complex but primarily mediated protein post-translational modifications (PTMs). Ubiquitylation one such PTM, which controls regulating localisation, turnover, protein-protein interactions intra-cellular signalling. Over past two decades, numerous ubiquitin (Ub) E3 ligases been identified play a crucial role not only initiation replication also efficient termination processes. In this review, we discuss our current understanding how different Ub (RNF168, TRAIP, HUWE1, TRIP12, FANCL, BRCA1, RFWD3) function pathological consequences arising from inheriting deleterious Ub-dependent response.

Language: Английский

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