Our study explores the complex dynamics of the integrated stress response (ISR) axis, highlighting PIM2 kinase's critical role and its interaction with the BCL2 protein family, uncovering key mechanisms of cell survival and tumor progression. Elevated PIM2 expression, a marker of various cancers, often correlates with disease aggressiveness. Using a model of normal and malignant plasma cells, we show that inhibiting PIM2 kinase inhibits phosphorylated BAD production and activates ISR-mediated NOXA expression. This shift towards MCL1 dependence underscores the synergy achieved through combined PIM/MCL1 inhibition, driven largely by ISR-mediated NOXA expression. In mouse xenograft models, dual targeting of PIM2 and MCL1 effectively controls tumor growth-a response reversed by ISR-specific inhibition and upregulation of genes linked to tumor cell dissemination. This work elucidates the molecular intricacies of PIM2 inhibition and its implications for cancer therapy, especially in tumors with elevated PIM2 expression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696207 | PMC |
| http://dx.doi.org/10.1038/s41467-024-55572-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression.
Nat Commun
January 2025
Université de Rennes 1, INSERM, Établissement Français du Sang de Bretagne, UMR_S1236, F-35043, Rennes, France.
Our study explores the complex dynamics of the integrated stress response (ISR) axis, highlighting PIM2 kinase's critical role and its interaction with the BCL2 protein family, uncovering key mechanisms of cell survival and tumor progression. Elevated PIM2 expression, a marker of various cancers, often correlates with disease aggressiveness. Using a model of normal and malignant plasma cells, we show that inhibiting PIM2 kinase inhibits phosphorylated BAD production and activates ISR-mediated NOXA expression.
View Article and Find Full Text PDFTargeting the BMI1-Noxa axis by Dioscin induces apoptosis in oral squamous cell carcinoma cells.
J Cancer
January 2025
School of Stomatology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
Article Synopsis
- Dioscin is a natural steroidal saponin that shows antitumor effects by triggering apoptosis in various cancers, particularly through the Noxa protein.
- The study found that Dioscin enhances Noxa expression by reducing BMI1 levels, leading to increased tumor cell death in oral squamous cell carcinoma (OSCC).
- Additionally, Dioscin demonstrates effective tumor suppression in animal models, offering potential new strategies for treating OSCC.
and in prostate cancer: from molecular pathways to therapeutic targets: a narrative review.
Transl Androl Urol
November 2024
Department of Urology, Second People's Hospital of China Three Gorges University, Yichang, China.
Background And Objective: Prostate cancer is a major cause of cancer-related morbidity and mortality in men globally. The pathogenesis involves complex interactions between genetic mutations and environmental factors, activating multiple signaling pathways, especially Wnt/β-catenin, PI3K/Akt, and NF-κB pathways. Tumor suppressor genes and are key inhibitors of these pathways, crucial in suppressing tumor growth and metastasis.
View Article and Find Full Text PDFNmrA homologs have been reported as conserved regulators of the nitrogen metabolite repression (NMR) in various fungi. Here, we identified a NmrA homolog in and reported its functions in nitrogen utilization, growth and development, and pathogenesis. VdNmrA interacts with AreA protein and regulates the expression of a typical NCR target, the formamidase gene.
View Article and Find Full Text PDFJapanese encephalitis virus infection induces mitochondrial-mediated apoptosis through the proapoptotic protein BAX.
Front Microbiol
October 2024
Research Center of Swine Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Article Synopsis
- The Japanese encephalitis virus (JEV) is a major cause of viral encephalitis in Asia and triggers cell apoptosis through mechanisms that are not fully understood.
- In this study, researchers used CRISPR/Cas9 to knockout the BAX gene in PK-15 cells, which decreased JEV proliferation by nearly 40%, while overexpressing BAX had the opposite effect.
- JEV infection led to significant upregulation of various pro-apoptotic factors and mitochondrial damage, accelerating apoptosis, but knocking out BAX mitigated these effects, providing insights into JEV's pathogenic mechanisms.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!