ArticleOncogenesis2021
Feedback activation of STAT3 limits the response to PI3K/AKT/mTOR inhibitors in PTEN-deficient cancer cells.
Article in Oncogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The trial behind it
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Who cites it
37 citing papers in PubMed, 50 citations in OpenAlex.
- Integrative Bioinformatics and Machine Learning Analysis Identifies Novel Molecular Biomarkers in Prostate Adenocarcinoma.International journal of molecular sciences · 2026Article
- Decoding the PI3K/Akt/mTOR-JAK/STAT signaling axis in multiple sclerosis: mechanistic crosstalk and therapeutic opportunities.Immunologic research · 2026Review
- Repurposing T-type calcium channel blocker lomerizine as a therapeutic strategy for glioblastoma.JCI insight · 2026Article
- ERK1/2 hijack STAT3 via Thr714 phosphorylation to suppress gene expression.Cell communication and signaling : CCS · 2026Article
- Intracellular Oxidant Levels Are Crucial for Cell Survival and JAK/STAT Signaling in Classical Hodgkin's Lymphoma.Antioxidants (Basel, Switzerland) · 2026Article
- Anoikis: To Die or Not to Die?International journal of molecular sciences · 2026Review
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- TET1 loss promotes malignant phenotypes in HeLa cells and is associated with altered PTEN-PI3K/AKT/mTOR signaling.Frontiers in oncology · 2026Article
- Targeting dual-specificity phosphatase 23 to overcome chemoresistance and stem cell-like behavior in non-small cell lung cancer cells.Scientific reports · 2025Article
- The role of probiotics in controlling oral biofilm formation and mitigating oral squamous-cell carcinoma risk.Archives of microbiology · 2025Review
- PTEN-mediated resistance in cancer: From foundation to future therapies.Toxicology reports · 2025Review
- The CRISPR-Cas revolution in head and neck cancer: a new era of targeted therapy.Functional & integrative genomics · 2025Review
- Domperidone Induces Apoptosis through Suppression of STAT3 Signaling in Human Renal Cancer Caki-2 Cells.Journal of cancer prevention · 2025Article
- PTEN-deficient, chromosomal instability colorectal cancer is hypersensitive to STAT3 inhibition.International journal of biological sciences · 2025Article
- Neuroprotective Effects of STAT3 Inhibitor on Hydrogen Peroxide-Induced Neuronal Cell Death via the ERK/CREB Signaling Pathway.Neurochemical research · 2024Article
- STAT3 blockade ameliorates LPS-induced kidney injury through macrophage-driven inflammation.Cell communication and signaling : CCS · 2024Article
- Review
- Comparing Redox and Intracellular Signalling Responses to Cold Plasma in Wound Healing and Cancer.Current issues in molecular biology · 2024Review
- PQR309, a dual PI3K/mTOR inhibitor, synergizes with gemcitabine by impairing the GSK-3β and STAT3/HSP60 signaling pathways to treat nasopharyngeal carcinoma.Cell death & disease · 2024Article
- Development and verification of a manganese metabolism- and immune-related genes signature for prediction of prognosis and immune landscape in gastric cancer.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
The PI3K/AKT/mTOR signaling pathway is constitutively active in PTEN-deficient cancer cells, and its targeted inhibition has significant anti-tumor effects. However, the efficacy of targeted therapies is often limited due to drug resistance. The relevant signaling pathways in PTEN-deficient cancer cells treated with the PI3K/mTOR inhibitor BEZ235 were screened using a phosphokinase array, and further validated following treatment with multiple PI3K/AKT/mTOR inhibitors or AKT knockdown. The correlation between PTEN expression levels and STAT3 kinase phosphorylation in the tissue microarrays of gastric cancer patients was analyzed by immunohistochemistry. Cell proliferation and clonogenic assays were performed on the suitably treated PTEN-deficient cancer cells. Cytokine arrays, small molecule inhibition and knockdown assays were performed to identify related factors. PTEN-deficient tumor xenografts were established in nude mice that were treated with PI3K/AKT/mTOR and/or STAT3 inhibitors. PTEN deficiency was positively correlated with low STAT3 activity. PI3K/mTOR inhibitors increased the expression and secretion of macrophage migration inhibitory factor (MIF) and activated the JAK1/STAT3 signaling pathway. Both cancer cells and in vivo tumor xenografts showed that the combined inhibition of PI3K/AKT/mTOR and STAT3 activity enhanced the inhibitory effect of BEZ235 on the proliferation of PTEN-deficient cancer cells. Our findings provide a scientific basis for a novel treatment strategy in cancer patients with PTEN deficiency.
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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.