ArticleThe Journal of biological chemistry2013
Regulation of the Src-PP2A interaction in tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Regulation of programmed death ligand 1 (PD-L1) expression by TNF-related apoptosis-inducing ligand (TRAIL) in triple-negative breast cancer cells.Molecular carcinogenesis · 2023Article
- Targeting PP2A for cancer therapeutic modulation.Cancer biology & medicine · 2022Review
- Phosphate and Endothelial Function: How Sensing of Elevated Inorganic Phosphate Concentration Generates Signals in Endothelial Cells.Advances in experimental medicine and biology · 2022Review
- Breast Cancer Metastasis.Advances in experimental medicine and biology · 2021Article
- Inorganic Phosphate (Pi) Signaling in Endothelial Cells: A Molecular Basis for Generation of Endothelial Microvesicles in Uraemic Cardiovascular Disease.International journal of molecular sciences · 2020Article
- Article
- Targeting PP2A inhibits the growth of triple-negative breast cancer cells.Cell cycle (Georgetown, Tex.) · 2020Article
- Developing TRAIL/TRAIL death receptor-based cancer therapies.Cancer metastasis reviews · 2018Review
- PP2A as the Main Node of Therapeutic Strategies and Resistance Reversal in Triple-Negative Breast Cancer.Molecules (Basel, Switzerland) · 2017Review
- Article
- Article
- p21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase.The Journal of biological chemistry · 2015Article
- Surviving at a Distance: Organ-Specific Metastasis.Trends in cancer · 2015Review
- Selective activators of protein phosphatase 5 target the auto-inhibitory mechanism.Bioscience reports · 2015Article
- LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential.Cancer biology & therapy · 2015Review
- Hepatocellular carcinoma: targeting of oncogenic signaling networks in TRAIL resistant cancer cells.Molecular biology reports · 2014Review
- The role of Cullin3-mediated ubiquitination of the catalytic subunit of PP2A in TRAIL signaling.Cell cycle (Georgetown, Tex.) · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in transformed and tumor cells but not in normal cells, making it a promising agent for cancer therapy. However, many cancer cells are resistant to TRAIL, and the underlying mechanisms are not fully understood. Here, we show that the regulation of the PP2A and Src interaction plays a critical role in TRAIL resistance. Specifically, we show that TRAIL treatment activates the tyrosine kinase Src, which subsequently phosphorylates caspase-8 at tyrosine 380, leading to the inhibition of caspase-8 activation. We also show that upon TRAIL treatment, Src, caspase-8, and PP2A/C (a catalytic subunit of the PP2A phosphatase) are redistributed into lipid rafts, a microdomain of the plasma membrane enriched with cholesterol, where PP2A dephosphorylates Src at tyrosine 418 and in turn inhibits caspase-8 phosphorylation. Furthermore, we find that TRAIL treatment causes PP2A/C degradation. These data suggest that the balance between Src-mediated caspase-8 phosphorylation and the inactivation of Src-mediated caspase-8 phosphorylation by PP2A determines the outcome of TRAIL treatment in breast cancer cells. Therefore, this work identifies a novel mechanism by which the interaction between PP2A and Src in the context of caspase-8 activation modulates TRAIL sensitivity in cancer cells.
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Registered trials
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