Stem Cells in Cancer: From Mechanisms to Therapeutic Strategies

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 538 - 538

Published: April 3, 2025

Stem cells have emerged as a pivotal area of research in the field oncology, offering new insights into mechanisms cancer initiation, progression, and resistance to therapy. This review provides comprehensive overview role stem cancer, focusing on (CSCs), their characteristics, implications for We discuss origin identification CSCs, tumorigenesis, metastasis, drug resistance, potential therapeutic strategies targeting CSCs. Additionally, we explore use normal therapy, tissue regeneration delivery vehicles anticancer agents. Finally, highlight challenges future directions cell cancer.

Language: Английский

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MARK2/MARK3 Kinases Are Catalytic Codependencies of YAP/TAZ in Human Cancer

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(12), P. 2471 - 2488

Published: July 25, 2024

The Hippo signaling pathway is commonly dysregulated in human cancer, which leads to a powerful tumor dependency on the YAP/TAZ transcriptional coactivators. Here, we used paralog co-targeting CRISPR screens identify kinases MARK2/3 as absolute catalytic requirements for function diverse carcinoma and sarcoma contexts. Underlying this observation direct MARK2/3-dependent phosphorylation of NF2 YAP/TAZ, effectively reverses suppressive activity module LATS1/2. To simulate targeting MARK2/3, adapted CagA protein from H. pylori inhibitor show can regress established tumors vivo. Together, these findings reveal co-dependencies cancer; targets that may allow pharmacology restores pathway-mediated suppression.

Language: Английский

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Inhibition of thioredoxin reductase 1 sensitizes glucose-starved glioblastoma cells to disulfidptosis

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

Language: Английский

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Unraveling the YAP1-TGFβ1 axis: a key driver of androgen receptor loss in prostate cancer-associated fibroblasts

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Abstract Due to their pivotal roles in tumor progression and therapy resistance, cancer-associated fibroblasts (CAF) are considered key therapeutic targets with loss of stromal androgen receptor (AR) a poorly understood hallmark aggressive prostate cancer (PCa). A paucity pre-clinical models however has hampered functional studies CAF heterogeneity. We demonstrate that our newly-generated biobank contains three FAP + -fibroblast subtypes, each unique molecular traits. Cultures an early-activated phenotype expressed the highest levels AR exhibited AR-dependent growth. Consistently, cells expressing early-activation markers co-expressed nuclear clinical specimens were enriched pre-neoplastic lesions/low-grade PCa. Conversely, myofibroblastic (myCAF), which low vitro vivo proliferatively-insensitive signaling modulation, constituted predominant subpopulation stromogenic high-grade PCa castration-resistant LACP9 patient-derived xenografts. Exacerbation myCAF state upon castration LAPC9-bearing hosts underscored these findings. Mechanistically, was driven by NFκB-TGFβ1-YAP1 axis, whose combined targeting synergistically repressed hallmarks impaired autophagic flux, effects potentiated enzalutamide resulting cell death. Collectively, findings provide mechanistic rationale for adjuvant YAP1-TGFβ axis improve patient outcomes.

Language: Английский

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Decellularized Human Amniotic Member Hydrogel Promotes Limbal Stem Cells Proliferation

Colloids and Surfaces B Biointerfaces, Journal Year: 2025, Volume and Issue: unknown, P. 114656 - 114656

Published: March 1, 2025

Allogeneic cultured limbal epithelial stem cell transplantation has shown variable clinical success in treating deficiency, low cases are likely due to insufficient quantity or functional impairment. In this study, we engineered a decellularized amniotic membrane hydrogel (dAM-gel) using freeze-thaw protocol designed retain extracellular matrix integrity. Post-processing, collagen content decreased modestly from 313.50 ± 27.89 μg/mg 284.8 14.82 (P = 0.08), while glycosaminoglycan levels shifted 7.20 1.66 6.28 0.55 0.27). Crucially, the achieved near-complete DNA removal (7.41 0.78 vs. 0.14 0.06 μg/mg) < 0.0001), ensuring minimal immunogenicity. Although dAM-gel demonstrates limited gelation capacity at lower concentrations, it achieves robust 14 mg/ml, completing process within 28.26 1.21 minutes. Furthermore, facilitates migration and proliferation of cells, particularly p63 + which known correlate with treatments. A plausible explanation for phenomenon is that contains high concentration agrin, cells preserving their stemness via Yap1-cyclin D1 signaling pathway. conclusion, derived presents therapeutic promise deficiency by enhancing maintaining phenotype.

Language: Английский

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Activation of YAP/TAZ by gut microbiota via Wnt/β-catenin signaling in cancer development

Academia molecular biology and genomics., Journal Year: 2025, Volume and Issue: 2(2)

Published: April 1, 2025

This review examines the role of gut microbiota in activation Wnt/β-catenin signaling pathway and its impact on cancer progression via YAP/TAZ activation. Yes-associated protein, YAP, is a transcriptional coactivator involved regulating gene expression cell proliferation by interacting with TEA domain (TEAD) transcription factor Hippo pathway. The an evolutionarily conserved that important for development tissue homeostasis but was described as driving oncogenic processes through activity. In this regard, metabolites drove tumor activating onto increased evidence. discusses recent studies modulation effect further pursues effects treatment prevention.

Language: Английский

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Targeting the Hippo Pathway in Breast Cancer: A Proteomic Analysis of Yes-Associated Protein Inhibition

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 3943 - 3943

Published: April 22, 2025

The dysregulation of the Hippo signaling pathway leads to aberrant activation oncogenic YAP and TAZ, driving tumor progression. In breast cancer, this disruption promotes proliferation metastasis. This study investigates effects CA3, a selective inhibitor, on proteome triple-negative cancer MDA-MB-231 luminal-A-like MCF7 cells. Proteomic changes were analyzed via nano-LC-MS/MS, while cytotoxicity, apoptosis, autophagy assessed through WST-1 assays, flow cytometry, Western blot analyses. Bioinformatics tools employed identify enriched pathways. cells exhibited an increased expression DNA repair proteins (p < 0.05), indicating compensatory response maintain genomic stability. contrast, showed downregulation factors 0.005). Additionally, metabolic reprogramming was apparent in 0.001). Apoptosis assays revealed rise cell death, cycle analysis indicated pronounced G1-phase arrest 0.01). Moreover, autophagic suppression particularly evident study, for first time, provides evidence that subtypes exhibit distinct dependencies YAP-driven pathways, revealing potential therapeutic vulnerabilities. Targeting alongside or combining inhibition with blockade luminal holds significant enhance treatment efficacy.

Language: Английский

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Long non-coding RNA LRTOR drives osimertinib resistance in non-small cell lung cancer by boosting YAP positive feedback loop

Drug Resistance Updates, Journal Year: 2025, Volume and Issue: unknown, P. 101245 - 101245

Published: April 1, 2025

The therapeutic efficacy of osimertinib (OSI) in EGFR-mutant lung cancer is ultimately limited by the onset acquired resistance, which mechanisms remain poorly understood. Here, we identify a novel long non-coding RNA, LRTOR, as key driver OSI resistance non-small cell (NSCLC). Clinical data indicate that elevated LRTOR expression correlates with poor prognosis OSI-resistant patients. Functionally, promotes tumor growth and confers both vitro vivo. Mechanistically, shields YAP from LATS-mediated phosphorylation at Ser127 Ser381, preventing its proteasomal degradation. Furthermore, facilitates interaction between KCMF1, promoting K63-linked ubiquitination, nuclear translocation YAP, formation YAP/TEAD1 transcriptional complex, turn triggers transcription establishing positive feedback loop amplifies oncogenic signaling consequently induces resistance. depletion siRNA restores sensitivity resistant tumors, demonstrated patient-derived organoid xenograft models. Our findings unveil central regulator NSCLC propose it promising prognostic target for overcoming cancer.

Language: Английский

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Identification of Pyrazolo-Piperidinone Derivatives Targeting Yap-Tead Interface 3 as Anticancer Agents Through Integrated Virtual Screening and Mass Spectrometry Proteomics

Published: Jan. 1, 2025

Language: Английский

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RBM39 Promotes Base Excision Repair to Facilitate the Progression of HCC by Stabilising OGG1 mRNA

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: May 13, 2025

ABSTRACT Targeting base excision repair (BER) has been an attractive strategy in cancer therapeutics. RNA‐binding motif protein 39 (RBM39) modulates the alternative splicing of numerous genes involved occurrence and progression. However, whether how RBM39 regulates BER hepatocellular carcinoma (HCC) remain unclear. Here, we found that under oxidative stress, degradation or knockdown decreased efficiency HCC cells using a well‐designed reporter. Further assays showed promoted cell proliferation, migration, invasion, enhancing survival inhibiting apoptosis. Mechanistically, interacted with mRNA essential glycosidase 8‐oxoguanine‐DNA glycosylase 1 (OGG1), thereby stabilising OGG1 mRNA. This turn increases expression promotes HCC. Moreover, data suggested degradation, combined damage, could be more effective for treatment than monotherapy, both vitro xenograft mice models. Overall, demonstrated regulated stabilisation improved efficiency, suggesting combining degradant indisulam oxidising agent KBrO 3 emerging treatment.

Language: Английский

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