ArticleProceedings of the National Academy of Sciences of the United States of America2014
Engineering ePTEN, an enhanced PTEN with increased tumor suppressor activities.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 97 citations in OpenAlex.
- Threonine 348 regulates the subcellular localization of PTEN.FEBS open bio · 2026Article
- Reconstitution of Ras-PI3Kγ membrane communication and feedback using light-induced signaling inputs.Nature communications · 2026Article
- Carbon Nanotube-Mediated Delivery of PTEN Variants: In Vitro Antitumor Activity in Breast Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- GRHL2-HER3 and E-cadherin mediate EGFR-bypass drug resistance in lung cancer cells.Frontiers in cell and developmental biology · 2024Article
- GxcM-Fbp17/RacC-WASP signaling regulates polarized cortex assembly in migrating cells via Arp2/3.The Journal of cell biology · 2023Article
- Nuclear PTEN's Functions in Suppressing Tumorigenesis: Implications for Rare Cancers.Biomolecules · 2023Review
- Structural and Dynamic Effects of PTEN C-Terminal Tail Phosphorylation.Journal of chemical information and modeling · 2022Article
- Kinetic Changes of Ptdins (3,4,5) P3 within Fast and Slow Turnover Rates of Focal Adhesion.Reports of biochemistry & molecular biology · 2022Article
- Interaction between S4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (VSP).Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Immunofluorescence Detection of Plasma Membranous PTEN in Cultured Cells.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Article
- The orchestrated signaling by PI3Kα and PTEN at the membrane interface.Computational and structural biotechnology journal · 2022Review
- Gradients of PI(4,5)PFrontiers in cell and developmental biology · 2022Article
- A Comparative Study to Visualize PtdIns(4,5) P2 and PtdIns(3,4,5) P3 in MDA-MB-231 Breast Cancer Cell Line.Reports of biochemistry & molecular biology · 2022Article
- Generating a new mouse model for nuclear PTEN deficiency by a single K13R mutation.Genes to cells : devoted to molecular & cellular mechanisms · 2021Article
- The structural basis of PTEN regulation by multi-site phosphorylation.Nature structural & molecular biology · 2021Article
- Electric signals counterbalanced posterior vs anterior PTEN signaling in directed migration of Dictyostelium.Cell & bioscience · 2021Article
- The mechanism of full activation of tumor suppressor PTEN at the phosphoinositide-enriched membrane.iScience · 2021Article
- The Polarized Redistribution of the Contractile Vacuole to the Rear of the Cell is Critical for Streaming and is Regulated by PI(4,5)P2-Mediated Exocytosis.Frontiers in cell and developmental biology · 2021Review
- The Loss of Nuclear PTEN Increases Tumorigenesis in a Preclinical Mouse Model for Hepatocellular Carcinoma.iScience · 2020Article
- Posttranslational Regulation and Conformational Plasticity of PTEN.Cold Spring Harbor perspectives in medicine · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The signaling lipid phosphatidylinositol (3,4,5)-trisphosphate (PIP3) is a key regulator of cell proliferation, survival, and migration and the enzyme that dephosphorylates it, phosphatase and tensin homolog (PTEN), is an important tumor suppressor. As excess PIP3 signaling is a hallmark of many cancers, its suppression through activation of PTEN is a potential cancer intervention. Using a heterologous expression system in which human PTEN-GFP is expressed in Dictyostelium cells, we identified mutations in the membrane-binding regulatory interface that increase the recruitment of PTEN to the plasma membrane due to enhanced association with PI(4,5)P2. We engineered these into an enhanced PTEN (ePTEN) with approximately eightfold increased ability to suppress PIP3 signaling. Upon expression in human cells, ePTEN decreases PIP3 levels in the plasma membrane; phosphorylation of AKT, a major downstream event in PIP3 signaling; and cell proliferation and migration. Thus, the activation of PTEN can readjust PIP3 signaling and may serve as a feasible target for anticancer therapies.
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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.