ArticleOncotarget2015
Overexpression of Bcl-2 induces STAT-3 activation via an increase in mitochondrial superoxide.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- CD47 blockade-driven necroptosis complements BCL-2 inhibition-driven apoptosis in lymphoid malignancies.Journal of hematology & oncology · 2026Article
- The Significance of STAT3 in Colonic Diseases: A Comprehensive Study of Pathological Roles and Therapeutic Implications.Cell biochemistry and biophysics · 2025Review
- Superoxide-mediated phosphorylation and stabilization of Mcl-1 by AKT underlie venetoclax resistance in hematologic malignancies.Leukemia · 2025Article
- STAT3 Regulates the Redox Profile in MDA-MB-231 Breast Cancer Cells.Cell biochemistry and biophysics · 2024Article
- WDR12/RAC1 axis promoted proliferation and anti-apoptosis in colorectal cancer cells.Molecular and cellular biochemistry · 2024Article
- The Estrogen-Autophagy Axis: Insights into Cytoprotection and Therapeutic Potential in Cancer and Infection.International journal of molecular sciences · 2024Review
- Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention.Revista brasileira de farmacognosia : orgao oficial da Sociedade Brasileira de Farmacognosia · 2023Review
- Anti-tumor activities ofJournal of ginseng research · 2021Article
- Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated Autoimmune Diseases.Frontiers in immunology · 2021Review
- Serine-70 phosphorylated Bcl-2 prevents oxidative stress-induced DNA damage by modulating the mitochondrial redox metabolism.Nucleic acids research · 2020Article
- Cell death through the ages: The ICDS 25th Anniversary Meeting.The FEBS journal · 2020Article
- Review
- The Regulatory Role of Rac1, a Small Molecular Weight GTPase, in the Development of Diabetic Retinopathy.Journal of clinical medicine · 2019Review
- miR-125b Upregulates miR-34a and Sequentially Activates Stress Adaption and Cell Death Mechanisms in Multiple Myeloma.Molecular therapy. Nucleic acids · 2019Article
- How does estrogen work on autophagy?Autophagy · 2019Review
- Emodin inhibits colon cancer by altering BCL-2 family proteins and cell survival pathways.Cancer cell international · 2019Article
- Rac GTPases in Hematological Malignancies.International journal of molecular sciences · 2018Review
- Nucleus, Mitochondrion, or Reticulum? STAT3 à La Carte.International journal of molecular sciences · 2018Review
- [Effects of simvastatin on aortic vascular endothelial cell apoptosis and Bcl-2 protein expression in a rat model of atherosclerosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017Article
- Pharmacological Rac1 inhibitors with selective apoptotic activity in human acute leukemic cell lines.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We recently reported a novel interaction between Bcl-2 and Rac1 and linked that to the ability of Bcl-2 to induce a pro-oxidant state in cancer cells. To gain further insight into the functional relevance of this interaction, we utilized computer simulation based on the protein pathway dynamic network created by Cellworks Group Inc. STAT3 was identified among targets that positively correlated with Rac1 and/or Bcl-2 expression levels. Validating this, the activation level of STAT3, as marked by p-Tyr705, particularly in the mitochondria, was significantly higher in Bcl-2-overexpressing cancer cells. Bcl-2-induced STAT3 activation was a function of GTP-loaded Rac1 and NADPH oxidase (Nox)-dependent increase in intracellular superoxide (O2•-). Furthermore, ABT199, a BH-3 specific inhibitor of Bcl-2, as well as silencing of Bcl-2 blocked STAT3 phosphorylation. Interestingly, while inhibiting intracellular O2•- blocked STAT3 phosphorylation, transient overexpression of wild type STAT3 resulted in a significant increase in mitochondrial O2•- production, which was rescued by the functional mutants of STAT3 (Y705F). Notably, a strong correlation between the expression and/or phosphorylation of STAT3 and Bcl-2 was observed in primary tissues derived from patients with different sub-sets of B cell lymphoma. These data demonstrate the presence of a functional crosstalk between Bcl-2, Rac1 and activated STAT3 in promoting a permissive redox milieu for cell survival. Results also highlight the potential utility of a signature involving Bcl-2 overexpression, Rac1 activation and STAT3 phosphorylation for stratifying clinical lymphomas based on disease severity and chemoresistance.
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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.