ArticleOncogene2015
Deletion of Pim kinases elevates the cellular levels of reactive oxygen species and sensitizes to K-Ras-induced cell killing.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 47 citations in OpenAlex.
- Pim1 Mitigates Heart Failure by Suppressing Ferroptosis Via Activation of the mTORC1/SLC7A11/GPX4 Axis.Journal of cardiovascular translational research · 2026Article
- Metabolic protein kinase signalling in neuroblastoma.Molecular metabolism · 2023Review
- Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis.Cell death & disease · 2022Article
- Synergistic PIM kinase and proteasome inhibition as a therapeutic strategy for MYC-overexpressing triple-negative breast cancer.Cell chemical biology · 2022Article
- PIM kinases inhibit AMPK activation and promote tumorigenicity by phosphorylating LKB1.Cell communication and signaling : CCS · 2021Article
- Natural antiviral compound silvestrol modulates human monocyte-derived macrophages and dendritic cells.Journal of cellular and molecular medicine · 2020Article
- Ferroptosis: Final destination for cancer?Cell proliferation · 2020Review
- Small-Molecule-Targeting Hairpin Loop of hTERT Promoter G-Quadruplex Induces Cancer Cell Death.Cell chemical biology · 2019Article
- Mechanisms Behind Resistance to PI3K Inhibitor Treatment Induced by the PIM Kinase.Molecular cancer therapeutics · 2018Article
- PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity.The Journal of clinical investigation · 2018Article
- Hypoxia-Inducible PIM Kinase Expression Promotes Resistance to Antiangiogenic Agents.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Cytoplasmic Irradiation Induces Metabolic Shift in Human Small Airway Epithelial Cells via Activation of Pim-1 Kinase.Radiation research · 2017Article
- KRas, ROS and the initiation of pancreatic cancer.Small GTPases · 2017Article
- Mitochondrial and Oxidative Stress-Mediated Activation of Protein Kinase D1 and Its Importance in Pancreatic Cancer.Frontiers in oncology · 2017Review
- Pim kinase inhibition sensitizes FLT3-ITD acute myeloid leukemia cells to topoisomerase 2 inhibitors through increased DNA damage and oxidative stress.Oncotarget · 2016Article
- Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis.Nature chemical biology · 2016Article
- PIM Kinase Inhibitors Kill Hypoxic Tumor Cells by Reducing Nrf2 Signaling and Increasing Reactive Oxygen Species.Molecular cancer therapeutics · 2016Article
- Intrinsic resistance to PIM kinase inhibition in AML through p38α-mediated feedback activation of mTOR signaling.Oncotarget · 2016Article
- Article
- PIM kinase (and Akt) biology and signaling in tumors.Pharmacology & therapeutics · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The Pim protein kinases contribute to transformation by enhancing the activity of oncogenic Myc and Ras, which drives significant metabolic changes during tumorigenesis. In this report, we demonstrate that mouse embryo fibroblasts (MEFs) lacking all three isoforms of Pim protein kinases, triple knockout (TKO), cannot tolerate the expression of activated K-Ras (K-Ras(G12V)) and undergo cell death. Transduction of K-Ras(G12V) into these cells markedly increased the level of cellular reactive oxygen species (ROS). The addition of N-acetyl cysteine attenuated ROS production and reversed the cytotoxic effects of K-Ras(G12V) in the TKO MEFs. The altered cellular redox state caused by the loss of Pim occurred as a result of lower levels of metabolic intermediates in the glycolytic and pentose phosphate pathways as well as abnormal mitochondrial oxidative phosphorylation. TKO MEFs exhibit reduced levels of superoxide dismutase (Sod), glutathione peroxidase 4 (Gpx4) and peroxiredoxin 3 (Prdx3) that render them susceptible to killing by K-Ras(G12V)-mediated ROS production. In contrast, the transduction of c-Myc into TKO cells can overcome the lack of Pim protein kinases by regulating cellular metabolism and Sod2. In the absence of the Pim kinases, c-Myc transduction permitted K-Ras(G12V)-induced cell growth by decreasing Ras-induced cellular ROS levels. These results demonstrate that the Pim protein kinases have an important role in regulating cellular redox, metabolism and K-Ras-stimulated cell growth.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.