Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Regulation of Spontaneous Intestinal Tumorigenesis Through the Adaptor Protein MyD88
Seth Rakoff-Nahoum and
Ruslan Medzhitov*
Inflammation is increasingly recognized as an important componentof tumorigenesis, although the mechanisms and pathways involvedare not well understood. Tumor development is regulated by productsof several modifier genes, but instructions for their tumor-specificexpression are currently unknown. We show that the signalingthrough the adaptor protein MyD88 has a critical role in spontaneoustumor development in mice with heterozygous mutation in theadenomatous polyposis coli (APC) gene. We found that MyD88-dependentsignaling controls the expression of several key modifier genesof intestinal tumorigenesis and has a critical role in bothspontaneous and carcinogen-induced tumor development. This studythus reveals the important role of an innate immune signalingpathway in intestinal tumorigenesis.
Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
* To whom correspondence should be addressed. E-mail: ruslan.medzhitov{at}yale.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Toby Lawrence, Thorsten Hageman, and Frances Balkwill (6 July 2007) Science317 (5834), 51.
[DOI: 10.1126/science.1146052] |Summary »|Full Text »|PDF »
In Science Signaling
EDITORS' CHOICE
L. Bryan Ray (10 July 2007) Sci. STKE2007 (394), tw246.
[DOI: 10.1126/stke.3942007tw246] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
MAIL Regulates Human Monocyte IL-6 Production.
S. Seshadri, Y. Kannan, S. Mitra, J. Parker-Barnes, and M. D. Wewers (2009)
J. Immunol.
183, 5358-5368
|Abstract »|Full Text »|PDF »
Phospholipase C{varepsilon} promotes intestinal tumorigenesis of ApcMin/+ mice through augmentation of inflammation and angiogenesis.
M. Li, H. Edamatsu, R. Kitazawa, S. Kitazawa, and T. Kataoka (2009)
Carcinogenesis
30, 1424-1432
|Abstract »|Full Text »|PDF »
Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability.
F. Colotta, P. Allavena, A. Sica, C. Garlanda, and A. Mantovani (2009)
Carcinogenesis
30, 1073-1081
|Abstract »|Full Text »|PDF »
Milk fat globule epidermal growth factor-8 blockade triggers tumor destruction through coordinated cell-autonomous and immune-mediated mechanisms.
M. Jinushi, M. Sato, A. Kanamoto, A. Itoh, S. Nagai, S. Koyasu, G. Dranoff, and H. Tahara (2009)
J. Exp. Med.
206, 1317-1326
|Abstract »|Full Text »|PDF »
Haploinsufficiency of Kruppel-Like Factor 5 Rescues the Tumor-Initiating Effect of the ApcMin Mutation in the Intestine.
B. B. McConnell, A. B. Bialkowska, M. O. Nandan, A. M. Ghaleb, F. J. Gordon, and V. W. Yang (2009)
Cancer Res.
69, 4125-4133
|Abstract »|Full Text »|PDF »
SAP-1 is a microvillus-specific protein tyrosine phosphatase that modulates intestinal tumorigenesis.
H. Sadakata, H. Okazawa, T. Sato, Y. Supriatna, H. Ohnishi, S. Kusakari, Y. Murata, T. Ito, U. Nishiyama, T. Minegishi, et al. (2009)
Genes Cells
14, 295-308
|Abstract »|Full Text »|PDF »
Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface.
S. Vaishnava, C. L. Behrendt, A. S. Ismail, L. Eckmann, and L. V. Hooper (2008)
PNAS
105, 20858-20863
|Abstract »|Full Text »|PDF »
The Innate Immune Receptor Nod1 Protects the Intestine from Inflammation-Induced Tumorigenesis.
G. Y. Chen, M. H. Shaw, G. Redondo, and G. Nunez (2008)
Cancer Res.
68, 10060-10067
|Abstract »|Full Text »|PDF »
Interleukin (IL) 1{beta} Induction of IL-6 Is Mediated by a Novel Phosphatidylinositol 3-Kinase-dependent AKT/I{kappa}B Kinase {alpha} Pathway Targeting Activator Protein-1.
