Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Corvinus, FM; Orth, C; Moriggl, R; Tsareva, SA; Wagner, S; Pfitzner, EB; Baus, D; Kaufmann, R; Huber, LA; Zatloukal, K; Beug, H; Ohlschager, P; Schutz, A; Halbhuber, KJ; Friedrich, K.
Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth.
NEOPLASIA. 2005; 7(6): 545-555. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG Google Scholar

 

Autor/innen der Med Uni Graz:
Zatloukal Kurt
Altmetrics:

Dimensions Citations:

Plum Analytics:
Number of Figures: 7
| | | | | | |
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.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Biopsy -
Blotting, Western -
Cell Differentiation -
Cell Line, Tumor -
Cell Proliferation -
Colonic Neoplasms - pathology
Colorectal Neoplasms - pathology
DNA - metabolism
Genes, Dominant - metabolism
Humans - metabolism
Immunohistochemistry - metabolism
Interleukin-6 - metabolism
Lymphocytes - cytology
Mice - cytology
Mice, Nude - cytology
Neoplasm Transplantation - cytology
Retroviridae - genetics
STAT3 Transcription Factor - metabolism
Signal Transduction - metabolism
Time Factors - metabolism

Find related publications in this database (Keywords)
colorectal cancer
JAK/STAT pathway
STAT3
xenograft
cell proliferation
© Meduni Graz Impressum