Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival
Open accessAbstract
Background: Constitutive activation of signal transducer and activator of transcription 3 (Stat3) signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer. Results: We found that elevated Stat3 phosphorylation in 19 of 100 (19%) bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F) and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC). The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin) and a cell cycle regulating gene (cyclin D1) was associated with the cell growth inhibition and apoptosis. Conclusion: These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.
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Aberrant STAT3 activation has been implicated in tumor initiation and progression, and preclinical evidence supports STAT3 as a potential treatment target in STAT3-dependent epithelial cancer.
“Aberrant STAT3 activation has been implicated in tumor initiation and progression, and preclinical evidence strongly supports STAT3 as a potential treatment target in STAT3-dependent epithelial cancer (1, 3, 46).”
From Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer (2022) · cites this paper as [46]
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- Authors
- Chen, C.-L., Cen, L., Kohout, J., Hutzen, B., Chan, C., Hsieh, F.-C., Loy, A., Huang, V., Cheng, G., & Lin, J.
- Affiliations
- Nationwide Children's Hospital (US)
- The Ohio State University (US)
- Corresponding author
- Lin, Jiayuh
- Venue
- Molecular Cancer
- Published
- 2008-10-21
- Volume
- 7
- Issue
- 1
- Pages
- 78-78
- ISSN
- 1476-4598 (ISSN-L)
- PMC
- PMC2577686
- OpenAlex
- W2156105549
- Cited by
- 125
- References
- 51
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 10 · 2022: 20 · 2021: 6 · 2020: 7 · 2019: 9 · 2018: 9 · 2017: 7 · 2016: 2 · 2015: 8 · 2014: 10 · 2013: 4 · 2012: 5
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Cancer (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ohio State University
- Nationwide Children's Hospital
- Research Institute, Nationwide Children's Hospital
- National Cancer Institute (R01CA096714)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- STAT3 signaling, bladder cancer, STAT3 phosphorylation, cell growth, cell survival, apoptosis, caspase-3, caspase-8, caspase-9, Bcl-2, Bcl-xL, survivin, cyclin D1, dominant-negative STAT3, adenoviral vector, anti-apoptotic genes, therapeutic target
- MeSH terms
- Adult, Aged, Aged, 80 and over, Urinary Bladder Neoplasms, Cell Survival, Female, Humans, Male, Middle Aged, Polycyclic Compounds, Signal Transduction, Apoptosis, Caspases, Cell Line, Tumor, STAT3 Transcription Factor
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