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Updated: Jun 2, 2026
In vitro Organoid Culture of Primary Mouse Colon Tumors
Published on: May 17, 2013
Stat3 is a negative regulator of intestinal tumor progression in Apc(Min) mice
Monica Musteanu1, Leander Blaas, Markus Mair
1Ludwig Boltzmann Institute for Cancer Research, A-1090 Vienna, Austria.
Background And Aims:
The transcription factor signal transducer and activator of transcription 3 (Stat3) has been considered to promote progression and metastasis of intestinal cancers.
Methods:
We investigated the role of Stat3 in intestinal tumors using mice with conditional ablation of Stat3 in intestinal epithelial cells (Stat3(DeltaIEC)).
Results:
In the Apc(Min) mouse model of intestinal cancer, genetic ablation of Stat3 reduced the multiplicity of early adenomas. However, loss of Stat3 promoted tumor progression at later stages, leading to formation of invasive carcinomas, which significantly shortened the lifespan of Stat3(DeltaIEC)Apc(Min/+) mice. Interestingly, loss of Stat3 in tumors of Apc(Min/+) mice had no significant impact on cell survival and angiogenesis, but promoted cell proliferation. A genome-wide expression analysis of Stat3-deficient tumors suggested that Stat3 might negatively regulate intestinal cancer progression via the cell adhesion molecule CEACAM1.
Conclusions:
Our data suggest that Stat3 impairs invasiveness of intestinal tumors. Therefore, therapeutic targeting of the Stat3 signaling pathway in intestinal cancer should be evaluated for adverse effects on tumor progression.
Insights
Signal transducer and activator of transcription 3 (Stat3) normally inhibits intestinal cancer invasion. Loss of Stat3 in mice paradoxically promoted invasive carcinomas and shortened lifespan, suggesting complex roles in tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Signal transducer and activator of transcription 3 (Stat3) is implicated in intestinal cancer progression and metastasis.
- Its precise role in different stages of intestinal tumorigenesis requires further elucidation.
Purpose of the Study:
- To investigate the role of Stat3 in intestinal tumor development and progression.
- To understand the impact of Stat3 ablation in intestinal epithelial cells on tumor characteristics and survival.
Main Methods:
- Utilized mice with conditional ablation of Stat3 in intestinal epithelial cells (Stat3(DeltaIEC)).
- Employed the Apc(Min) mouse model to study intestinal cancer.
- Performed genome-wide expression analysis on Stat3-deficient tumors.
Main Results:
- Genetic ablation of Stat3 reduced early adenoma multiplicity but promoted invasive carcinoma formation in Apc(Min) mice.
- Loss of Stat3 accelerated tumor progression and shortened lifespan in Stat3(DeltaIEC)Apc(Min/+) mice.
- Stat3 deficiency promoted cell proliferation without affecting cell survival or angiogenesis, potentially via CEACAM1 regulation.
Conclusions:
- Stat3 appears to impair the invasiveness of intestinal tumors.
- Targeting the Stat3 signaling pathway in intestinal cancer warrants careful evaluation for potential adverse effects on tumor progression.
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