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

Overview

Journal Neoplasia

Publisher Elsevier

Specialty Oncology

Date 2005 Jul 23

PMID 16036105

Citations 198

Authors

Florian M Corvinus

Carina Orth

Richard Moriggl

Svetlana A Tsareva

Stefan Wagner

Edith B Pfitzner

Daniela Baus

Roland Kaufmann

Lukas A Huber

Kurt Zatloukal

Hartmut Beug

Peter Ohlschlager

Alexander Schutz

Karl-Jurgen Halbhuber

Karlheinz Friedrich

Affiliations

Soon will be listed here.

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.

Citing Articles

Targeting STAT3 with SH-4-54 suppresses stemness and chemoresistance in cancer stem-like cells derived from colorectal cancer.

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Long non-coding RNAs (lncRNAs) in cancer development: new insight from STAT3 signaling pathway to immune evasion.

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