Constitutive Activation of Stat3 Signaling Confers Resistance to Apoptosis in Human U266 Myeloma Cells
Open accessAbstract
Interleukin 6 (IL-6) is the major survival factor for myeloma tumor cells and induces signaling through the STAT proteins. We report that one STAT family member, Stat3, is constitutively activated in bone marrow mononuclear cells from patients with multiple myeloma and in the IL-6-dependent human myeloma cell line U266. Moreover, U266 cells are inherently resistant to Fas-mediated apoptosis and express high levels of the antiapoptotic protein Bcl-xL. Blocking IL-6 receptor signaling from Janus kinases to the Stat3 protein inhibits Bcl-xL expression and induces apoptosis, demonstrating that Stat3 signaling is essential for the survival of myeloma tumor cells. These findings provide evidence that constitutively activated Stat3 signaling contributes to the pathogenesis of multiple myeloma by preventing apoptosis.
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STAT3-mediated upregulation of Bcl-xL, Bcl-2, and Mcl-1 contributes to apoptosis evasion in several cancers.
“STAT3-mediated upregulation of Bcl-xL, Bcl-2, and Mcl-1 contributes to apoptosis evasion in several cancers.77–79”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [78]
The Discussion (page not supplied) links STAT3-induced Bcl-xL expression to resistance to apoptosis in myeloma cells. The passage describing the Stat3β experiment (indexed as Abstract; page not supplied) says Bcl-2 levels were not substantially reduced when STAT3 signaling was blocked, and the copy does not establish STAT3-mediated Mcl-1 upregulation. The demonstrated mechanism is in myeloma cells, not several cancers. (LLM, conf=0.89)
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- Authors
- Catlett-Falcone, R., Landowski, T. H., Oshiro, M. M., Turkson, J., Levitzki, A., Savino, R., Ciliberto, G., Moscinski, L., Fernández-Luna, J. L., Nuñez, G., Dalton, W. S., & Jove, R.
- Affiliations
- University of South Florida (US)
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Jove, Richard
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 10
- Issue
- 1
- Pages
- 105-115
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2118310862
- Cited by
- 1,638
- References
- 3
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 23 · 2023: 34 · 2022: 23 · 2021: 37 · 2020: 40 · 2019: 41 · 2018: 28 · 2017: 52 · 2016: 50 · 2015: 60 · 2014: 70 · 2013: 86 · 2012: 86
- FWCI
- 37.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA077859, R01CA055652, CA-55652, CA77859)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- STAT3 signaling, multiple myeloma, U266 cells, apoptosis resistance, Fas-mediated apoptosis, Bcl-xL, interleukin-6, IL-6 receptor, Janus kinase, constitutive activation, myeloma cell survival
- MeSH terms
- Animals, Antineoplastic Agents, DNA-Binding Proteins, Gene Expression Regulation, Humans, Immunity, Innate, Multiple Myeloma, Promoter Regions, Genetic, Protein-Tyrosine Kinases, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Signal Transduction, Trans-Activators, 3T3 Cells, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Receptors, Interleukin-6, Tyrphostins, STAT3 Transcription Factor, bcl-X Protein, Mice
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