Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88.
Inflammation is increasingly recognized as an important component of tumorigenesis, although the mechanisms and pathways involved are not well understood. Tumor development is regulated by products of several modifier genes, but instructions for their tumor-specific expression are currently unknown. We show that the signaling through the adaptor protein MyD88 has a critical role in spontaneous tumor development in mice with heterozygous mutation in the adenomatous polyposis coli (APC) gene. We found that MyD88-dependent signaling controls the expression of several key modifier genes of intestinal tumorigenesis and has a critical role in both spontaneous and carcinogen-induced tumor development. This study thus reveals the important role of an innate immune signaling pathway in intestinal tumorigenesis.
Rakoff-Nahoum
Seth
S
Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Medzhitov
Ruslan
R
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D007113:Immunity, Innate; D007414:Intestinal Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D007420:Intestine, Large / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88