ArticleOncotarget2016
Expression of the p66Shc protein adaptor is regulated by the activator of transcription STAT4 in normal and chronic lymphocytic leukemia B cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Trial
- Taginostat, a new quinolone-based HDAC6 inhibitor, promotes apoptosis of chronic lymphocytic leukemia cells in vitro and in vivo by activating STAT4.Apoptosis : an international journal on programmed cell death · 2026Article
- The Role of p66Shc in Cancer: Molecular Mechanisms and Therapeutic Implications.Journal of cellular and molecular medicine · 2025Review
- p66Shc deficiency in CLL cells enhances PD-L1 expression and suppresses immune synapse formation.Frontiers in cell and developmental biology · 2024Article
- The miR-141/200c-STAT4 Axis Contributes to Leukemogenesis by Enhancing Cell Proliferation in T-PLL.Cancers · 2023Article
- p66Shc Deficiency in Chronic Lymphocytic Leukemia Promotes Chemokine Receptor Expression Through the ROS-Dependent Inhibition of NF-κB.Frontiers in oncology · 2022Article
- LncRNA Hmrhl regulates expression of cancer related genes in chronic myelogenous leukemia through chromatin association.NAR cancer · 2021Article
- Of Lymph Nodes and CLL Cells: Deciphering the Role of CCR7 in the Pathogenesis of CLL and Understanding Its Potential as Therapeutic Target.Frontiers in immunology · 2021Review
- CCR7 in Blood Cancers - Review of Its Pathophysiological Roles and the Potential as a Therapeutic Target.Frontiers in oncology · 2021Review
- P66Shc: A Pleiotropic Regulator of B Cell Trafficking and a Gatekeeper in Chronic Lymphocytic Leukemia.Cancers · 2020Review
- STAT4: an immunoregulator contributing to diverse human diseases.International journal of biological sciences · 2020Review
- Regulation of Selective B Cell Autophagy by the Pro-oxidant Adaptor p66SHC.Frontiers in cell and developmental biology · 2020Review
- p66Shc deficiency sets the scene for clinically aggressive chronic lymphocytic leukemia.Haematologica · 2019Article
- p66Shc deficiency in the Eμ-TCL1 mouse model of chronic lymphocytic leukemia enhances leukemogenesis by altering the chemokine receptor landscape.Haematologica · 2019Article
- Boosting chemokine receptor recycling: an elixir of life for chronic lymphocytic leukemia.Oncotarget · 2018Article
- The pro-oxidant adaptor p66SHC promotes B cell mitophagy by disrupting mitochondrial integrity and recruiting LC3-II.Autophagy · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
p66Shc attenuates mitogenic, prosurvival and chemotactic signaling and promotes apoptosis in lymphocytes. Consistently, p66Shc deficiency contributes to the survival and trafficking abnormalities of chronic lymphocytic leukemia (CLL) B cells. The mechanism of p66shc silencing in CLL B cells is methylation-independent, at variance with other cancer cell types. Here we identify STAT4 as a novel transcriptional regulator of p66Shc in B cells. Chromatin immunoprecipitation and reporter gene assays showed that STAT4 binds to and activates the p66shc promoter. Silencing or overexpression of STAT4 resulted in a co-modulation of p66Shc. IL-12-dependent STAT4 activation caused a coordinate increase in STAT4 and p66Shc expression, which correlated with enhanced B cell apoptosis. Treatment with the STAT4 inhibitor lisofylline reverted partly this effect, suggesting that STAT4 phosphorylation is not essential for but enhances p66shc transcription. Additionally, we demonstrate that CLL B lymphocytes have a STAT4 expression defect which partly accounts for their p66Shc deficiency, as supported by reconstitution experiments. Finally, we show that p66Shc participates in a positive feedback loop to promote STAT4 expression. These results provide new insights into the mechanism of p66Shc expression in B cells and its defect in CLL, identifying the STAT4/IL-12 pathway as a potential therapeutic target in this neoplasia.
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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.