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- Title
Gut microbiota accelerate tumor growth via c-jun and STAT3 phosphorylation in APCMin/+ mice.
- Authors
Li, Yinghui; Kundu, Parag; Seow, Shih Wee; de Matos, Cristina Teixeira; Aronsson, Linda; Chin, Keh Chuang; Kärre, Klas; Pettersson, Sven; Greicius, Gediminas
- Abstract
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 APCMin/+ 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 APCMin/+ mice.
- Subjects
TUMOR growth; PHOSPHORYLATION; LABORATORY mice; GUT microbiome; COLON cancer; GROWTH factors; ERYTHROPOIESIS
- Publication
Carcinogenesis, 2012, Vol 33, Issue 6, p1231
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgs137