Gut microbiota accelerate tumor growth via c-jun and STAT3 phosphorylation in APCMin/+ mice
| Autor: | Shih Wee Seow, Cristina Teixeira de Matos, Keh Chuang Chin, Klas Kärre, Gediminas Greicius, Yat Li, Linda Aronsson, Sven Pettersson, Parag Kundu |
|---|---|
| Přispěvatelé: | School of Biological Sciences |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
STAT3 Transcription Factor Cancer Research Genes APC Lipopolysaccharide Mice Transgenic Inflammation Gut flora Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor medicine Animals Myeloid Cells Intestinal Mucosa Phosphorylation STAT3 Erythropoietin Cell Proliferation 030304 developmental biology 0303 health sciences CD11b Antigen biology Cell growth Macrophages c-jun JNK Mitogen-Activated Protein Kinases Anemia General Medicine biology.organism_classification Tumor Burden 3. Good health Science::Biological sciences [DRNTU] Intestines Mice Inbred C57BL chemistry Cell culture 030220 oncology & carcinogenesis Immunology biology.protein Cancer research Metagenome Signal transduction medicine.symptom Colorectal Neoplasms Signal Transduction |
| Zdroj: | Carcinogenesis |
| Popis: | Chronic inflammation is increasingly recognized as a major contributor of human colorectal cancer (CRC). While gut microbiota can trigger inflammation in the intestinal tract, the precise signaling pathways through which host cells respond to inflammatory bacterial stimulation are unclear. Here, we show that gut microbiota enhances intestinal tumor load in the APC(Min/+) mouse model of CRC. Furthermore, systemic anemia occurs coincident with rapid tumor growth, suggesting a role for intestinal barrier damage and erythropoiesis-stimulating mitogens. Short-term stimulation assays of murine colonic tumor cells reveal that lipopolysaccharide, a microbial cell wall component, can accelerate cell growth via a c-Jun/JNK activation pathway. Colonic tumors are also infiltrated by CD11b+ myeloid cells expressing high levels of phospho-STAT3 (p-Tyr705). Our results implicate the role of gut microbiota, through triggering the c-Jun/JNK and STAT3 signaling pathways in combination with anemia, in the acceleration of tumor growth in APC(Min/+) mice. |
| Databáze: | OpenAIRE |
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