TY  - JOUR
A1  - Corvinus, Florian Matthias
A1  - Orth, Carina
A1  - Moriggl, Richard
A1  - Tsareva, Svetlana
A1  - Wagner, Stefan
A1  - Pfitzner, Edith
A1  - Baus, Daniela
A1  - Kaufmann, Roland
A1  - Huber, Lukas A.
A1  - Zatloukal, Kurt
A1  - Beug, Hartmut
A1  - Öhlschläger, Peter
A1  - Schütz, Alexander
A1  - Halbhuber, Karl-Jürgen
A1  - Friedrich, Karlheinz
T1  - Persistent stat3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth
T2  - Neoplasia
N2  - 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.
KW  - Colorectal cancer
KW  - JAWSTAT pathway
KW  - STAT3
KW  - xenograft
KW  - cell proliferation
Y1  - 2005
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/55105
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-551058
SN  - 1476-5586
SN  - 1522-8002
N1  - Under a Creative Commons license
VL  - 7
IS  - 6
SP  - 545
EP  - 555
PB  - Stockton Press
CY  - Basingstoke
ER  -