ArticleOncotarget2016
Phosphorylation of Notch1 by Pim kinases promotes oncogenic signaling in breast and prostate cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- A systematic review on active sites and functions of PIM-1 protein.Human cell · 2022Pooled it
- Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.Cell communication and signaling : CCS · 2026Review
- Disrupting Notch signalling by a small molecule inhibiting dihydroorotate dehydrogenase activity.Scientific reports · 2026Article
- Computational Modelling Strategies for Exploring Triazolopyridazine PIM1 Kinase Inhibitors as Anticancer Agents.Anti-cancer agents in medicinal chemistry · 2025Article
- AKT1-Mediated NOTCH1 phosphorylation promotes gastric cancer progression via targeted regulation of IRS-1 transcription.Journal of cancer research and clinical oncology · 2024Article
- Endothelial Pim3 kinase protects the vascular barrier during lung metastasis.Nature communications · 2024Article
- PIM1 kinase and its diverse substrate in solid tumors.Cell communication and signaling : CCS · 2024Review
- PIM3 Kinase: A Promising Novel Target in Solid Cancers.Cancers · 2024Review
- Regulation of Notch1 Signalling by Long Non-Coding RNAs in Cancers and Other Health Disorders.International journal of molecular sciences · 2023Review
- Potential role of PIM1 inhibition in the treatment of SARS-CoV-2 infection.Journal, genetic engineering & biotechnology · 2023Article
- Targeting Pim kinases in hematological cancers: molecular and clinical review.Molecular cancer · 2023Review
- Antitumor activity of the protein kinase inhibitor 1-(β-D-2'-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines.BMC cancer · 2022Article
- Roles of Notch Signaling in the Tumor Microenvironment.International journal of molecular sciences · 2022Review
- Comprehensive Diagnostic Medical System Based on Notch1 Signaling Pathway to Inhibit the Growth of Small-Cell Lung Carcinoma.Journal of healthcare engineering · 2022Article
- Pathogenesis and treatment of multiple myeloma bone disease.The Japanese dental science review · 2021Review
- PIM Kinases in Multiple Myeloma.Cancers · 2021Review
- Crystal Structure-Guided Design of Bisubstrate Inhibitors and Photoluminescent Probes for Protein Kinases of the PIM Family.Molecules (Basel, Switzerland) · 2021Article
- PIM kinases inhibit AMPK activation and promote tumorigenicity by phosphorylating LKB1.Cell communication and signaling : CCS · 2021Article
- Identification of PIM1 substrates reveals a role for NDRG1 phosphorylation in prostate cancer cellular migration and invasion.Communications biology · 2021Article
- PIM1 accelerates prostate cancer cell motility by phosphorylating actin capping proteins.Cell communication and signaling : CCS · 2020Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumorigenesis is a multistep process involving co-operation between several deregulated oncoproteins. In this study, we unravel previously unrecognized interactions and crosstalk between Pim kinases and the Notch signaling pathway, with implications for both breast and prostate cancer. We identify Notch1 and Notch3, but not Notch2, as novel Pim substrates and demonstrate that for Notch1, the serine residue 2152 is phosphorylated by all three Pim family kinases. This target site is located in the second nuclear localization sequence (NLS) of the Notch1 intracellular domain (N1ICD), and is shown to be important for both nuclear localization and transcriptional activity of N1ICD. Phosphorylation-dependent stimulation of Notch1 signaling promotes migration of prostate cancer cells, balances glucose metabolism in breast cancer cells, and supports in vivo growth of both types of cancer cells on chick embryo chorioallantoic membranes. Furthermore, Pim-induced growth of orthotopic prostate xenografts in mice is associated with enhanced nuclear Notch1 activity. Finally, simultaneous inhibition of Pim and Notch abrogates the cellular responses more efficiently than individual treatments, opening up new vistas for combinatorial cancer therapy.
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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.