title: Gut microbiota accelerate tumor growth via c-jun and STAT3 phosphorylation in APCMin/+ mice.
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 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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Parag
authors.initials: P
authors.lastname: Kundu
authors.forename: Shih Wee
authors.initials: SW
authors.lastname: Seow
authors.forename: Cristina Teixeira
authors.initials: CT
authors.lastname: de Matos
authors.forename: Linda
authors.initials: L
authors.lastname: Aronsson
authors.forename: Keh Chuang
authors.initials: KC
authors.lastname: Chin
authors.forename: Klas
authors.initials: K
authors.lastname: Kärre
authors.forename: Sven
authors.initials: S
authors.lastname: Pettersson
authors.forename: Gediminas
authors.initials: G
authors.lastname: Greicius
mesh_terms: D000740:Anemia; D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D004921:Erythropoietin / Q000494:pharmacology; D017491:Genes, APC; D007249:Inflammation / Q000382:microbiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology* / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D054892:Metagenome / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000378:metabolism; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D047368:Tumor Burden
chemical_list: D039481:CD11b Antigen; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D004921:Erythropoietin; D048031:JNK Mitogen-Activated Protein Kinases