Molecular Insights on Signaling Cascades in Breast Cancer: A Comprehensive Review

Cancers, Год журнала: 2025, Номер 17(2), С. 234 - 234

Опубликована: Янв. 13, 2025

The complex signaling network within the breast tumor microenvironment is crucial for its growth, metastasis, angiogenesis, therapy escape, stem cell maintenance, and immunomodulation. An array of secretory factors their receptors activate downstream cascades regulating cancer progression metastasis. Among various pathways, EGFR, ER, Notch, Hedgehog pathways have recently been identified as in terms proliferation, survival, differentiation, maintenance CSCs, failure. These mediate such MAPK, including MEK/ERK that promote common pro-oncogenic signaling, whereas dysregulation PI3K/Akt, Wnt/β-catenin, JAK/STAT activates key oncogenic events drug resistance, CSC enrichment, metabolic reprogramming. Additionally, these orchestrate an intricate interplay between stromal cells, immune cells. Metabolic reprogramming adaptations contribute to aggressive are unresponsive therapy. Herein, recent insights into novel operating TME aid advancement emphasized current developments practices targeting enhance treatment efficacy reviewed.

Язык: Английский

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Triple-Negative Breast Cancer Progression and Drug Resistance in the Context of Epithelial–Mesenchymal Transition

Cancers, Год журнала: 2025, Номер 17(2), С. 228 - 228

Опубликована: Янв. 12, 2025

Triple-negative breast cancer (TNBC) is one of the most difficult subtypes to treat due its distinct clinical and molecular characteristics. Patients with TNBC face a high recurrence rate, an increased risk metastasis, lower overall survival compared other subtypes. Despite advancements in targeted therapies, traditional chemotherapy (primarily using platinum compounds taxanes) continues be standard treatment for TNBC, often limited long-term efficacy. tumors are heterogeneous, displaying diverse mutation profile considerable chromosomal instability, which complicates therapeutic interventions. The development chemoresistance frequently associated process epithelial–mesenchymal transition (EMT), during epithelial tumor cells acquire mesenchymal-like phenotype. This shift enhances metastatic potential, while simultaneously reducing effectiveness chemotherapeutics. It has also been suggested that EMT plays central role stem cells. Hence, there growing interest exploring small-molecule inhibitors target as future strategy overcoming resistance improving outcomes patients TNBC. review focuses on progression drug emphasis these processes. We present TNBC-specific EMT-related features, key protein markers, various signaling pathways involved. discuss important mechanisms factors related within context EMT, highlighting improve patients’ outcomes.

Язык: Английский

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CBX1 is involved in hepatocellular carcinoma progression and resistance to sorafenib and lenvatinib via IGF-1R/AKT/SNAIL signaling pathway

Hepatology International, Год журнала: 2024, Номер 18(5), С. 1499 - 1515

Опубликована: Май 20, 2024

Abstract Background Chromobox Homolog 1 (CBX1) plays a crucial role in the pathogenesis of numerous diseases, including evolution and advancement diverse cancers. The CBX1 pan-cancer its mechanism hepatocellular carcinoma (HCC), however, remains to be further investigated. Methods Bioinformatics approaches were harnessed scrutinize CBX1’s expression profile, association with tumor staging, potential impact on patient outcomes across various Single-cell RNA sequencing data facilitated investigation patterns at individual cell level. levels HCC adjacent non-tumor tissues quantified through Real-Time Polymerase Chain Reaction (RT-PCR), Western Blotting (WB), Immunohistochemical analyses. A tissue microarray was employed explore relationship between levels, prognosis, clinicopathological characteristics HCC. Various vitro assays—including CCK-8, colony formation, Transwell invasion, scratch tests—were conducted assess proliferative motility properties cells upon modulation expression. Moreover, functional discerned xenograft studies nude mice. Results found upregulated most cancer forms, heightened correlating adverse prognoses. Within context HCC, elevated consistently indicative poorer clinical outcomes. Suppression knockdown methodologies markedly diminished proliferation, invasive capabilities, migratory activity, Epithelial−mesenchymal transition (EMT) processes, resistance Tyrosine kinase inhibitors (TKIs). Contrastingly, augmentation opposite effects. Subsequent investigative efforts revealed promoter EMT contributor increased TKI within cells, mediated via IGF-1R/AKT/SNAIL signaling axis. oncogenic activities proved attenuable either by AKT pathway inhibition or targeted silencing IGF-1R. Conclusions broad overexpression specifically positions it as putative entity. It is implicated forwarding progression exacerbating interaction cascade.

Язык: Английский

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Targeting TGFβ receptor-mediated snail and twist: WSG, a polysaccharide from Ganoderma lucidum, and it-based dissolvable microneedle patch suppress melanoma cells

Carbohydrate Polymers, Год журнала: 2024, Номер 341, С. 122298 - 122298

Опубликована: Май 20, 2024

Язык: Английский

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Cross-Talk between the TGF-β and Cell Adhesion Signaling Pathways in Cancer

International Journal of Medical Sciences, Год журнала: 2024, Номер 21(7), С. 1307 - 1320

Опубликована: Янв. 1, 2024

Transforming growth factor-β (TGF-β) is strongly associated with the cell adhesion signaling pathway in differentiation, migration, etc. Mechanistically, TGF-β secreted an inactive form and localizes to extracellular matrix (ECM) via latent binding protein (LTBP). However, it release of mature that essential for activation pathway. This progress requires specific integrins (one main groups molecules (CAMs)) recognize activate dormant TGF-β. In addition, regulates ability through modulating CAMs expression. The aberrant pathway, caused by abnormal expression key regulatory (such as Smad proteins, certain transcription factors, non-coding RNAs), promotes tumor invasive metastasis epithelial-mesenchymal transition (EMT) during late stages tumorigenesis. this paper, we summarize crosstalk between cancer its underlying molecular mechanisms.

Язык: Английский

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Computational Identification of ECT2 as a Potential Pan-Cancer Biomarker and Therapeutic Target Through Integrated Genomic Data Analysis

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

The ECT2 gene, encoding a guanine nucleotide exchange factor, plays crucial roles in cell cycle progression and cytoskeletal dynamics, implicating its involvement various cancers. However, comprehensive pan-cancer analysis integrating genomic data is still lacking. This study employed an integrated approach using from multiple cancer genomics databases to assess across malignancies. Expression profiles of were analyzed for differential expression tumor stages association with clinical outcomes. Correlation analyses examined the relationship between immune infiltration levels. Pathway enrichment identified biological processes influenced by dysregulation progression. These methods facilitated exploration ECT2's role biology, revealing potential implications diagnosis, prognosis, therapy. Analysis 33 types consistently shows elevated expression. correlates staging eight cancers molecular subtypes 13 cancers, associations 22 suggesting modulation. demonstrates strong diagnostic (AUC > 0.9) 16 poorer overall survival 11 positively MSI STAD, MESO, UCEC, READ, negatively DLBC; it TMB PAAD, ACC, LGG, LUAD, THYM. also exhibits diverse correlations checkpoint genes specific through CIBERSORT analysis. interacts proteins like RACGAP1, KIF23, enriched pathways involving polarity, Ras signaling, tight junctions, impacting stemness types. offers insights into biology integrative bioinformatics analyses. results advocate as biomarker therapeutic target malignancies, avenues personalized oncology strategies.

Язык: Английский

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Epithelial to Mesenchymal Transition in the Endometrium Mediated by HOXA10 drives Embryo Implantation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Abstract Embryo implantation requires the breaching of endometrial luminal epithelium (LE) to facilitate invasion. In this study, we report that during implantation, LE cells undergo partial epithelial-to-mesenchymal transition (pEMT) specifically at sites. This pEMT in is critical, as vivo knockdown EMT transcription factor Twist 2 inhibits embryo implantation. Furthermore, observed a reduction expression HOXA10 Interestingly, HOXA10-hypomorphic mice and human epithelial (RL95-2) with ( KD) also acquire migratory phenotype vitro , suggesting loss drives epithelium. The KD have higher score differential genes associated cell migration TGF-β signaling pathways. We determined genome-wide occupancy sites identified 1,246 direct targets had significant roles EMT. Collectively, our findings suggest required maintain an state its activates mesenchymal resulting phenotype. adds member MET inducer team engage mutually inhibitory feedback loops directly or indirectly team. summary, study establishes critical step for reveals regulates process.

Язык: Английский

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Regulation of epithelial growth factor receptors by the oncoprotein E5 during the HPV16 differentiation-dependent life cycle

Tumour Virus Research, Год журнала: 2025, Номер 19, С. 200315 - 200315

Опубликована: Март 7, 2025

Human papillomavirus (HPV) 16 infection initiates upon viral entry into the basal cells of epithelium. The virus manipulates signaling pathways to complete its life cycle, which depends on cellular differentiation. expresses oncoproteins E5, E6, and E7 promote immune evasion, cell cycle progression, apoptosis inhibition, replication. least studied oncoprotein is E5 (16E5), can regulate epithelial growth factor receptor (GFR) pathways. GFRs such as transforming factor-beta (TGFBR), epidermal (EGFR), keratinocyte (KGFR) have essential roles in growth, differentiation, proliferation. These receptors obtain their ligands from microenvironment, once activated, behavior therefore represent valuable targets for establish maintain a environment supportive infection. ability 16E5 proliferation differentiation varies through differentiating epithelium, making it necessary adequately describe association between GFRs. Here we summarize regulation GFR by 16E5, discuss stromal factors, outline unresolved questions over during HPV cycle.

Язык: Английский

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Molecular mechanisms and signaling pathways related to brain metastasis in breast cancer

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 27, 2025

Brain metastasis in breast cancer (BCBM) significantly threatens the survival and quality of life patients, particularly those with triple-negative (TNBC) HER2-positive subtypes. It involves complex molecular mechanisms diverse signaling pathways. This review highlights recent research on pathways BCBM. The process BCBM includes several key steps: local infiltration cells into bloodstream subsequent spread to brain. They must then overcome blood-brain barrier (BBB) establish grow Multiple pathways, including PI3K/AKT, STAT3, NF-κB, Notch, Wnt are involved this process. Overall, is a disease regulated by multiple To improve patient life, it crucial deepen explore new treatment targets strategies. will enhance our understanding lead more effective treatments.

Язык: Английский

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Echinatin inhibits the growth and metastasis of Human hepatocellular carcinoma cells through p38 and JNK signaling pathways

Tissue and Cell, Год журнала: 2025, Номер 95, С. 102907 - 102907

Опубликована: Апрель 6, 2025

Язык: Английский

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