Florian Matthias Corvinus, Carina Orth, Richard Moriggl, Svetlana Tsareva, Stefan Wagner, Edith Pfitzner, Daniela Baus, Roland Kaufmann, Lukas A. Huber, Kurt Zatloukal, Hartmut Beug, Peter Öhlschläger, Alexander Schütz, Karl-Jürgen Halbhuber, Karlheinz Friedrich
- 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 CRCderived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.
MetadatenVerfasserangaben: | Florian Matthias Corvinus, Carina Orth, Richard Moriggl, Svetlana Tsareva, Stefan Wagner, Edith PfitznerORCiDGND, Daniela Baus, Roland KaufmannGND, Lukas A. Huber, Kurt Zatloukal, Hartmut Beug, Peter Öhlschläger, Alexander Schütz, Karl-Jürgen Halbhuber, Karlheinz Friedrich |
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URN: | urn:nbn:de:hebis:30:3-551058 |
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DOI: | https://doi.org/10.1593/neo.04571 |
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ISSN: | 1476-5586 |
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ISSN: | 1522-8002 |
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Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/16036105 |
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Titel des übergeordneten Werkes (Englisch): | Neoplasia |
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Verlag: | Stockton Press |
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Verlagsort: | Basingstoke |
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Dokumentart: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Jahr der Fertigstellung: | 2005 |
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Jahr der Erstveröffentlichung: | 2005 |
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Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Datum der Freischaltung: | 20.07.2020 |
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Freies Schlagwort / Tag: | Colorectal cancer; JAWSTAT pathway; STAT3; cell proliferation; xenograft |
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Jahrgang: | 7 |
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Ausgabe / Heft: | 6 |
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Seitenzahl: | 11 |
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Erste Seite: | 545 |
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Letzte Seite: | 555 |
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Bemerkung: | Under a Creative Commons license |
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HeBIS-PPN: | 467516316 |
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Institute: | Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus |
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DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Lizenz (Deutsch): | Creative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0 |
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