ArticleCell communication and signaling : CCS2019
Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- A systematic review on active sites and functions of PIM-1 protein.Human cell · 2022Pooled it
- Exploring PIM1 Kinase as a Therapeutic Target: Mechanisms and Strategies in Cancer Treatment.International journal of molecular sciences · 2026Review
- Dysregulation of the inside-out signaling pathway in CNS-infiltrated pediatric T-cell acute lymphoblastic leukemia.Research square · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Suppressing CDCA8/CDK1 improves oral squamous cell carcinoma by modulating proliferation, apoptosis, cell cycle and migration.Discover oncology · 2025Article
- TMED3 promotes prostate cancer via FOXO1a and FOXO3a phosphorylation.Oncology research · 2025Article
- Development and Evaluation of ABI-171, a New Fluoro-Catechin Derivative, for the Treatment of Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2024Article
- PIM1 kinase and its diverse substrate in solid tumors.Cell communication and signaling : CCS · 2024Review
- Integrating intracellular and extracellular proteomic profiling for in-depth investigations of cellular communication in a model of prostate cancer.Proteomics · 2023Article
- The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis.Cellular & molecular biology letters · 2023Article
- Inhibition of PIM Kinases Promotes Neuroblastoma Cell Differentiation to a Neuronal Phenotype.Journal of pediatric surgery · 2023Article
- Targeting Pim kinases in hematological cancers: molecular and clinical review.Molecular cancer · 2023Review
- The Role of PIM Kinases in Pediatric Solid Tumors.Cancers · 2022Review
- Crystal Structure-Guided Design of Bisubstrate Inhibitors and Photoluminescent Probes for Protein Kinases of the PIM Family.Molecules (Basel, Switzerland) · 2021Article
- Osteopontin isoform c promotes the survival of cisplatin-treated NSCLC cells involving NFATc2-mediated suppression on calcium-induced ROS levels.BMC cancer · 2021Article
- DGG-100629 inhibits lung cancer growth by suppressing the NFATc1/DDIAS/STAT3 pathway.Experimental & molecular medicine · 2021Article
- NFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.PloS one · 2021Article
- Crucial Roles of microRNA-Mediated Autophagy in Urologic Malignancies.International journal of biological sciences · 2021Review
- PIM1 accelerates prostate cancer cell motility by phosphorylating actin capping proteins.Cell communication and signaling : CCS · 2020Article
- PIM1 inhibitor synergizes the anti-tumor effect of osimertinib via STAT3 dephosphorylation in EGFR-mutant non-small cell lung cancer.Annals of translational medicine · 2020Article
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProgression of prostate cancer from benign local tumors to metastatic carcinomas is a multistep process. Here we have investigated the signaling pathways that support migration and invasion of prostate cancer cells, focusing on the role of the NFATC1 transcription factor and its post-translational modifications. We have previously identified NFATC1 as a substrate for the PIM1 kinase and shown that PIM1-dependent phosphorylation increases NFATC1 activity without affecting its subcellular localization. Both PIM kinases and NFATC1 have been reported to promote cancer cell migration, invasion and angiogenesis, but it has remained unclear whether the effects of NFATC1 are phosphorylation-dependent and which downstream targets are involved.
methodsWe used mass spectrometry to identify PIM1 phosphorylation target sites in NFATC1, and analysed their functional roles in three prostate cancer cell lines by comparing phosphodeficient mutants to wild-type NFATC1. We used luciferase assays to determine effects of phosphorylation on NFAT-dependent transcriptional activity, and migration and invasion assays to evaluate effects on cell motility. We also performed a microarray analysis to identify novel PIM1/NFATC1 targets, and validated one of them with both cellular expression analyses and in silico in clinical prostate cancer data sets.
resultsHere we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells. We observed that also PIM2 and PIM3 can phosphorylate NFATC1, and identified several novel putative PIM1/NFATC1 target genes. These include the ITGA5 integrin, which is differentially expressed in the presence of wild-type versus phosphorylation-deficient NFATC1, and which is coexpressed with PIM1 and NFATC1 in clinical prostate cancer specimens.
conclusionsBased on our data, phosphorylation of PIM1 target sites stimulates NFATC1 activity and enhances its ability to promote prostate cancer cell migration and invasion. Therefore, inhibition of the interplay between PIM kinases and NFATC1 may have therapeutic implications for patients with metastatic forms of cancer.
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