Constitutively activated Stat3 protects fibroblasts from serum withdrawal and UV-induced apoptosis and antagonizes the proapoptotic effects of activated Stat1
Open accessAbstract
Stats1 and 3 (signal transducers and activators of transcription) can be activated simultaneously, although not necessarily to the same degree or duration, by the interaction of cells with the same polypeptide ligand (EGF, PDGF, or high concentrations of IL-6, for example). However, these two Stat proteins can mediate opposing effects on cell growth and survival. Stat1 activation slows growth and promotes apoptosis. In contrast, activated Stat3 can protect cells from apoptosis. Furthermore, a constitutively active form of Stat3, Stat3-C (bridged by S-S linkages between cysteines instead of phosphotyrosines) can induce cellular transformation of fibroblasts. We have determined that fibroblasts transformed by Stat3-C are more resistant to proapoptotic stimuli than nontransformed cells. Also, to examine the potential opposing roles in apoptosis of Stat1 and Stat3, we studied the cervical carcinoma-derived cell line, Me180, which undergoes Stat1-dependent, IFNγ-induced apoptosis. Me180 cells that express Stat3-C are protected against IFNγ-mediated apoptosis.
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STAT3 activation seems to be protective against UV.
“STAT3 activation seems to be protective (Shen et al., 2001; Chan et al., 2004b; Sano et al., 2005; Aziz et al., 2007a; Barry et al., 2010; Bito et al., 2010a,b).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Shen et al., 2001
STAT3 is activated by UV through DNA damage and reactive oxygen species.
“STAT3 also is activated by UV through DNA damage and reactive oxygen species (Shen et al., 2001; Aziz et al., 2007a; Barry et al., 2010; Bito et al., 2010b).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Shen et al., 2001
The Results section on fibroblasts transformed by Stat3-C reports that cells expressing constitutively activated Stat3 were relatively resistant to UV-induced apoptosis. It does not report that UV activates Stat3, or that DNA damage or reactive oxygen species mediate such activation; searches for those mechanisms found no supporting passage in our copy. (LLM, conf=0.76)
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“STAT3 also is activated by UV through DNA damage and reactive oxygen species (Shen et al., 2001; Aziz et al., 2007a; Barry et al., 2010; Bito et al., 2010b).”
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- Authors
- Shen, Y., Devgan, G., Darnell, J. E., & Bromberg, J. F.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Laboratory of Molecular Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021; and Department of Medicine, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, NY 10021
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-02-06
- Volume
- 98
- Issue
- 4
- Pages
- 1543-1548
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC29293
- OpenAlex
- W2051638902
- Cited by
- 249
- References
- 3
- Citations by year
- 2025: 4 · 2022: 7 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 8 · 2016: 7 · 2015: 7 · 2014: 9 · 2013: 5 · 2012: 8
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- James S. McDonnell Foundation
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI032489, AI32489)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- STAT3, STAT1, apoptosis, fibroblasts, serum deprivation, UV-induced apoptosis, interferon-gamma, ME180 cells, cervical cancer, cell transformation, cytokine signaling
- MeSH terms
- Animals, Cell Line, Transformed, DNA-Binding Proteins, Fibroblasts, Growth Inhibitors, Humans, Interferon-gamma, Proto-Oncogene Proteins, Tumor Cells, Cultured, Ultraviolet Rays, Signal Transduction, Trans-Activators, Oncogene Protein pp60(v-src), 3T3 Cells, Culture Media, Serum-Free, Apoptosis, Proto-Oncogene Proteins c-bcl-2, STAT1 Transcription Factor, STAT3 Transcription Factor, bcl-X Protein, bcl-2-Associated X Protein, Mice
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