ArticleJournal of immunology (Baltimore, Md. : 1950)2015
PTEN is a negative regulator of NK cell cytolytic function.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 43 citations in OpenAlex.
- Pancreatic ductal adenocarcinoma: integrating molecular insights for targeted interventions.Signal transduction and targeted therapy · 2026Review
- Genome-wide CRISPR screens identify critical targets to enhance CAR-NK cell antitumor potency.Cancer cell · 2025Article
- TIGIT Affects CAR NK-cell Effector Function in the Solid Tumor Microenvironment by Modulating Immune Synapse Strength.Cancer immunology research · 2025Article
- Dysregulation of lncRNAs in NK cells from breast cancer patients: implications for NK cell functions.Immunogenetics · 2025Article
- Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.International journal of molecular sciences · 2025Review
- QTL Mapping-Based Identification of Visceral White-Nodules Disease Resistance Genes inInternational journal of molecular sciences · 2024Article
- Natural killer cells for pancreatic cancer immunotherapy: Role of nanoparticles.Cancer letters · 2023Article
- Signaling Pathways Leading to mTOR Activation Downstream Cytokine Receptors in Lymphocytes in Health and Disease.International journal of molecular sciences · 2023Review
- Integrating somatic CNV and gene expression in breast cancers from women with PTEN hamartoma tumor syndrome.NPJ genomic medicine · 2023Article
- Etiology of end-stage liver cirrhosis impacts hepatic natural killer cell heterogenicity.Frontiers in immunology · 2023Article
- PGE2 inhibits neutrophil phagocytosis through the EP2R-cAMP-PTEN pathway.Immunity, inflammation and disease · 2022Article
- Akt isoforms in the immune system.Frontiers in immunology · 2022Review
- Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.Frontiers in oncology · 2022Review
- Review
- Transcription Factors Associated With IL-15 Cytokine Signaling During NK Cell Development.Frontiers in immunology · 2021Review
- Review
- PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy.International journal of molecular sciences · 2020Review
- Pharmacological targeting of natural killer cells for cancer immunotherapy.Cancer science · 2020Review
- ZebrafishVaccines · 2020Article
- The Role of PTEN in Innate and Adaptive Immunity.Cold Spring Harbor perspectives in medicine · 2019Review
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 1 country.
Funding
Abstract
Human NK cells are characterized by their ability to initiate an immediate and direct cytolytic response to virally infected or malignantly transformed cells. Within human peripheral blood, the more mature CD56(dim) NK cell efficiently kills malignant targets at rest, whereas the less mature CD56(bright) NK cells cannot. In this study, we show that resting CD56(bright) NK cells express significantly more phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein when compared with CD56(dim) NK cells. Consistent with this, forced overexpression of PTEN in NK cells resulted in decreased cytolytic activity, and loss of PTEN in CD56(bright) NK cells resulted in elevated cytolytic activity. Comparable studies in mice showed PTEN overexpression did not alter NK cell development or NK cell-activating and inhibitory receptor expression yet, as in humans, did decrease expression of downstream NK activation targets MAPK and AKT during early cytolysis of tumor target cells. Confocal microscopy revealed that PTEN overexpression disrupts the NK cell's ability to organize immunological synapse components including decreases in actin accumulation, polarization of the microtubule organizing center, and the convergence of cytolytic granules. In summary, our data suggest that PTEN normally works to limit the NK cell's PI3K/AKT and MAPK pathway activation and the consequent mobilization of cytolytic mediators toward the target cell and suggest that PTEN is among the active regulatory components prior to human NK cells transitioning from the noncytolytic CD56(bright) NK cell to the cytolytic CD56(dim) NK cells.
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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.