The DOI matches its Crossref record; 53 of the 59 references it cites were found in a registry or an index.
Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth
Open accessAbstract
Colorectal carcinoma (CRC) is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRC-derived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.
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“IL-6 via STAT-3 has been shown to promote tumor cell proliferation in many cancers, including oral squamous cell carcinoma via DNA hypomethylation (31), prostate cancer through androgen receptor activation (32), and colon cancer (33).”
From Tumor-Induced Inflammatory Cytokines and the Emerging Diagnostic Devices for Cancer Detection and Prognosis (2021) · cites this paper as [33]
In the citing paper
“Constitutive STAT3 signaling has been implicated in aberrant cell growth and proliferation in many cancers, including head and neck squamous cell carcinoma, colorectal carcinoma, melanoma, glioblastoma multiforme, multiple myeloma, non-small cell lung cancer, and others.58,69–73”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [69]
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Cites
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Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality
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6 of the 59 references couldn’t be matched to a known paper.
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Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors
Siveen, K. S., Sikka, S., Surana, R., Dai, X., Zhang, J., Kumar, A. P., Tan, B. K. H., Sethi, G., & Bishayee, A. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2013.12.005 · Cited by 645
Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis
Gibbs, C. P., Kukekov, V. G., Reith, J. D., Tchigrinova, O., Suslov, O. N., Scott, E. W., Ghivizzani, S. C., Ignatova, T. N., & Steindler, D. A. (2005) · Neoplasia · doi:10.1593/neo.05394 · Cited by 492
Tumor exosomes inhibit differentiation of bone marrow dendritic cells
Yu, S., Liu, C., Su, K., Wang, J., Liu, Y., Zhang, L., Li, C., Cong, Y., Kimberly, R., Grizzle, W. E., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.6867 · Cited by 425
Molecular Pathways Involved in Colorectal Cancer: Implications for Disease Behavior and Prevention
Colussi, D., Brandi, G., Bazzoli, F., & Ricciardiello, L. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140816365 · Cited by 429
Interleukin-6 - A Key Regulator of Colorectal Cancer Development
Waldner, M. J., Foersch, S., & Neurath, M. F. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.4614 · Cited by 434
Metadata
- Authors
- Corvinus, F. M., Orth, C., Moriggl, R., Tsareva, S. A., Wagner, S., Pfitzner, E. B., Baus, D., Kaufman, R., Huber, L. A., Zatloukal, K., Beug, H., Öhlschläger, P., Schütz, A., Halbhuber, K.-J., & Friedrich, K.
- Affiliations
- Friedrich Schiller University Jena (DE)
- Research Institute of Molecular Pathology (AT)
- Georg Speyer Haus (DE)
- Universität Innsbruck (AT)
- University of Graz (AT)
- Leipzig University (DE)
- Corresponding author
- Friedrich, Karlheinz
- Venue
- Neoplasia
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 7
- Issue
- 6
- Pages
- 545-555
- ISSN
- 1476-5586 (ISSN-L)
- PMC
- PMC1501283
- OpenAlex
- W2014737409
- Cited by
- 427
- References
- 59
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 27 · 2023: 21 · 2022: 28 · 2021: 40 · 2020: 29 · 2019: 22 · 2018: 15 · 2017: 27 · 2016: 24 · 2015: 30 · 2014: 24 · 2013: 30 · 2012: 17
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neoplasia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- STAT3, colorectal cancer, constitutive STAT3 activation, interleukin-6, cell proliferation, tumor growth, tumor microenvironment, tumor xenografts, dominant-negative STAT3, therapeutic target, infiltrating lymphocytes
- MeSH terms
- Animals, Biopsy, Cell Differentiation, Colonic Neoplasms, DNA, Genes, Dominant, Humans, Immunohistochemistry, Lymphocytes, Mice, Nude, Neoplasm Transplantation, Retroviridae, Time Factors, Blotting, Western, Colorectal Neoplasms, Signal Transduction, Interleukin-6, Cell Line, Tumor, Cell Proliferation, STAT3 Transcription Factor, Mice
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