Cited by 433Cytokine Signaling Pathways and InteractionsTGF-β signaling in diseasesGrowth Hormone and Insulin-like Growth Factors

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Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth

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Corvinus, Florian M., Orth, Carina, Moriggl, Richard, Tsareva, Svetlana A., Wagner, Stefan, Pfitzner, Edith B., Baus, Daniela, Kaufman, Roland, Huber, Lukas A., Zatloukal, Kurt, Beug, Hartmut, Öhlschläger, Peter, Schütz, Alexander, Halbhuber, Karl-Jürgen, Friedrich, Karlheinz·2005·Neoplasia

DOI 10.1593/neo.04571PMC PMC1501283

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Abstract

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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The role of cytokines in the pathogenesis of malignant neoplasms
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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
ORCID: Moriggl, Richard
Pfitzner, Edith B.
Huber, Lukas A.
Zatloukal, Kurt
Venue: Neoplasia
Publisher: Elsevier BV
Published: 2005-06
Volume: 7
Issue: 6
Pages: 545-555
ISSN: 1476-5586 (ISSN-L)
DOI: 10.1593/neo.04571
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: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 3260 d)
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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Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth

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