ArticleOncogene2016
Activation of nuclear PTEN by inhibition of Notch signaling induces G2/M cell cycle arrest in gastric cancer.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Pooled it
- Antineoplastic effect of piperine compared with doxorubicin via suppressing γ-secretase/notch pathway in breast cancer cells.Discover oncology · 2026Article
- Profillin-1 and Transgelin-2: Actin Binding Proteins Expression in Early and Advanced Stages of Triple-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.Cancer reports (Hoboken, N.J.) · 2026Article
- Increasing expression of presenilin 1, β-catenin, and p-PTEN and its regulatory roles on cell invasion in gastric cancer.World journal of gastrointestinal oncology · 2026Article
- EZH2 inhibition and 5-azacytidine enhance antitumor immunity in PTEN-deficient glioblastoma by activation viral mimicry response.Journal for immunotherapy of cancer · 2025Article
- PTEN inhibition enhances sensitivity of ovarian cancer cells to the poly (ADP-ribose) polymerase inhibitor by suppressing the MRE11-RAD50-NBN complex.British journal of cancer · 2024Article
- miR-101-3p-mediated role of PDZK1 in hepatocellular carcinoma progression and the underlying PI3K/Akt signaling mechanism.Cell division · 2024Article
- Article
- Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.Experimental & molecular medicine · 2023Article
- Article
- The Regulation of Cyclins and Cyclin-Dependent Kinases in the Development of Gastric Cancer.International journal of molecular sciences · 2023Review
- Histone methyltransferase SETD1A interacts with notch and promotes notch transactivation to augment ovarian cancer development.BMC cancer · 2023Article
- LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1.Cancer cell international · 2022Article
- The TGFβ/Notch axis facilitates Müller cell-to-epithelial transition to ultimately form a chronic glial scar.Molecular neurodegeneration · 2021Article
- NACK and INTEGRATOR act coordinately to activate Notch-mediated transcription in tumorigenesis.Cell communication and signaling : CCS · 2021Article
- Article
- Review
- MTFR2, A Potential Biomarker for Prognosis and Immune Infiltrates, Promotes Progression of Gastric Cancer Based on Bioinformatics Analysis and Experiments.Journal of Cancer · 2021Article
- Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications.Frontiers in molecular biosciences · 2021Review
- ATM Kinase Inhibition Preferentially Sensitises PTEN-Deficient Prostate Tumour Cells to Ionising Radiation.Cancers · 2020Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutation in PTEN has not yet been detected, but its function as a tumor suppressor is inactivated in many cancers. In this study we determined that, activated Notch signaling disables PTEN by phosphorylation and thereby contributes to gastric tumorigenesis. Notch inhibition by small interfering RNA or γ-secretase inhibitor (GSI) induced mitotic arrest and apoptosis in gastric cancer cells. Notch inhibition induced dephosphorylation in the C-terminal domain of PTEN, which led to PTEN nuclear localization. Overexpression of activated Notch1-induced phosphorylation of PTEN and reversed GSI-induced mitotic arrest. Dephosphorylated nuclear PTEN caused prometaphase arrest by interaction with the cyclin B1-CDK1 complex, resulting in their accumulation in the nucleus and subsequent apoptosis. We found a correlation between high expression levels of Notch1 and low survival rates and, similarly, between reduced nuclear PTEN expression and increasing the TNM classification of malignant tumours stages in malignant tissues from gastric cancer patients. The growth of Notch1-depleted gastric tumors was significantly retarded in xenografted mice, and in addition, PTEN deletion restored growth similar to control tumors. We also demonstrated that combination treatment with GSI and chemotherapeutic agents significantly reduced the orthotopically transplanted gastric tumors in mice without noticeable toxicity. Overall, our findings suggest that inhibition of Notch signaling can be employed as a PTEN activator, making it a potential target for gastric 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.