Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Enhancement of cellular senescence in tumours triggers a stable cell growth arrest and activation of an antitumour immune response that can be exploited for cancer therapy. Currently, there are only a limited number of targeted therapies that act by increasing senescence in cancers, but the majority of them are not selective and also target healthy cells. Here we developed a chemogenomic screening to identify compounds that enhance senescence in PTEN-deficient cells without affecting normal cells. By using this approach, we identified casein kinase 2 (CK2) as a pro-senescent target. Mechanistically, we show that Pten loss increases CK2 levels by activating STAT3. CK2 upregulation in Pten null tumours affects the stability of Pml, an essential regulator of senescence. However, CK2 inhibition stabilizes Pml levels enhancing senescence in Pten null tumours. Taken together, our screening strategy has identified a novel STAT3-CK2-PML network that can be targeted for pro-senescence therapy for cancer.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/ncomms8227 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Autophagy inhibitors block pathogenic NET release in immune-mediated inflammatory disease without impairing host defence.
Rheumatology (Oxford)
August 2025
Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool UK.
Objectives: Activation of neutrophils and release of neutrophil extracellular traps (NETs), proteases and reactive oxygen species (ROS) is pathogenic in immune-mediated inflammatory diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), driving inflammation and damaging host tissues. The aim of this research was to identify small molecule inhibitors of NET production using a highly-curated panel of narrow-spectrum small molecule kinase inhibitors termed the Kinase Chemogenomic Set (KCGS).
Methods: Neutrophils were isolated from healthy controls (HC) and people with RA or SLE.
Inhibiting the RNA helicase DDX3X in Burkitt lymphoma induces oxydative stress and impedes tumor progression in xenografts.
Front Cell Dev Biol
July 2025
Institut de Recherches Cliniques de Montréal (IRCM), Université de Montréal, Montréal, QC, Canada.
Introduction: Burkitt Lymphoma (BL), an aggressive B-cell lymphoma driven by MYC translocations, requires intensive chemotherapy treatments which deliver high effectiveness yet increase future risks of developing secondary malignancies. We have previously shown that DDX3X, an RNA helicase frequently mutated in BL, is essential for B cell lymphomagenesis in mice.
Methods And Results: To assess if DDX3X could therefore represent a promising therapeutic target for BL, we tested two DDX3X inhibitors, the well characterized RK-33 and the more potent newly developed C1, in three BL cell lines (CA46, Raji, Daudi).
A cationic amphiphilic drug synergizes with strobilurin fungicides to control fungal-borne plant diseases.
Cell Chem Biol
June 2025
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:
Fungal phytopathogens are responsible for major losses in agricultural yields annually. While the use of topical fungicides remains key to managing agricultural pathogens, the emergence of drug-resistant strains necessitates identifying additional treatment options. In this study, we performed an in vitro small molecule screen against the devastating cereal pathogen Fusarium graminearum, identifying CMLD009688 as a priority growth inhibitor.
View Article and Find Full Text PDFDecoding post-transcriptional regulatory networks by RNA-linked CRISPR screening in human cells.
Nat Methods
June 2025
Basic Sciences Division and Computational Biology Section of the Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
RNAs undergo a complex choreography of metabolic processes that are regulated by thousands of RNA-associated proteins. Here we introduce ReLiC, a scalable and high-throughput RNA-linked CRISPR approach to measure the responses of diverse RNA metabolic processes to knockout of 2,092 human genes encoding all known RNA-associated proteins. ReLiC relies on an iterative strategy to integrate genes encoding Cas9, single-guide RNAs (sgRNAs) and barcoded reporter libraries into a defined genomic locus.
View Article and Find Full Text PDFDrug Combinations Targeting FAK and MEK Overcomes Tumor Heterogeneity in Glioblastoma.
Pharmaceutics
April 2025
Edinburgh Cancer Research, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK.
: Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options and poor prognosis, largely owing to its heterogeneity and the involvement of multiple intracellular signaling pathways that contribute to drug resistance. While recent advancements in targeted drug combination therapies, such as dabrafenib and trametinib, show promise for certain GBM subgroups, identifying effective drug combinations across the broader GBM population remains a challenge. Integrin-mediated signaling, particularly through Focal Adhesion Kinase (FAK), plays a pivotal role in GBM pathogenesis and invasion, making it a potential therapeutic target and component of future drug combination strategies.
View Article and Find Full Text PDF