ArticleMolecular cell2021
Regulation of PTEN translation by PI3K signaling maintains pathway homeostasis.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 132 citations in OpenAlex.
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- Cutaneous gain-of-function mutation of LRIG3 leads to alopecia by upregulation of ERBB, PI3K/AKT, NOTCH1 signaling pathways.Scientific reports · 2026Article
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- Modulatory effects of traditional Chinese medicine and derived active metabolites on autoimmune-inflammatory signaling pathways in multiple sclerosis: a narrative review.Frontiers in pharmacology · 2026Review
- Therapeutic advances in HR+/HER2- advanced breast cancer after failure of CDK4/6 inhibitor therapy.Frontiers in oncology · 2026Review
- PI3K/AKT/mTOR axis in vascular malformations: from molecular insights to targeted clinical trials.Orphanet journal of rare diseases · 2025Review
- BMP-7 Treatment Ameliorates PTEN-Akt Mediated Apoptosis and Adverse Cardiac Remodeling in Ponatinib-Induced Cardiotoxicity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Evolution and Co-occurrence of PI3K Pathway Gene Mutations in Endometrial Carcinoma Molecular Subtypes at the Single-Cell Level.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Geniposide Inhibits Oral Squamous Cell Carcinoma by Regulating PI3K-Akt Signaling-Mediated Apoptosis: A Multi-Method Validation Study.Current issues in molecular biology · 2025Article
- Exploring Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) as a Potential Therapeutic Target for Cardiac Hypertrophy.ACS pharmacology & translational science · 2025Review
- Colorectal Cancer Cells-Derived Exosomal PIK3CA Mutation DNA Promotes Tumor Metastasis by Activating Fibroblast and Affecting Tumor Metastatic Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Metabolomics integrated genomics approach: Understanding multidrug resistance phenotype in MCF-7 breast cancer cells exposed to doxorubicin and ABCA1/EGFR/PI3k/PTEN crosstalk.Toxicology reports · 2025Article
- Mechanism of β‑sitosterol in treating keloids: Network pharmacology, molecular docking and experimental verification.Molecular medicine reports · 2025Article
- The Influence of AQP5 on the Response to Hydrogen Peroxide in Breast Cancer Cell Lines.International journal of molecular sciences · 2025Article
- Review
- Progressive Alcohol-Related Brain Atrophy and White Matter Pathology Are Linked to Long-Term Inhibitory Effects on mTOR Signaling.Biomolecules · 2025Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The PI3K pathway regulates cell metabolism, proliferation, and migration, and its dysregulation is common in cancer. We now show that both physiologic and oncogenic activation of PI3K signaling increase the expression of its negative regulator PTEN. This limits the duration of the signal and output of the pathway. Physiologic and pharmacologic inhibition of the pathway reduces PTEN and contributes to the rebound in pathway activity in tumors treated with PI3K inhibitors and limits their efficacy. Regulation of PTEN is due to mTOR/4E-BP1-dependent control of its translation and is lost when 4E-BP1 is deleted. Translational regulation of PTEN is therefore a major homeostatic regulator of physiologic PI3K signaling and plays a role in reducing the pathway activation by oncogenic PIK3CA mutants and the antitumor activity of PI3K pathway inhibitors. However, pathway output is hyperactivated in tumor cells with coexistent PI3K mutation and loss of PTEN function.
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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.