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Publication : A cell-intrinsic role for TLR2-MYD88 in intestinal and breast epithelia and oncogenesis.

First Author  Scheeren FA Year  2014
Journal  Nat Cell Biol Volume  16
Issue  12 Pages  1238-48
PubMed ID  25362351 Mgi Jnum  J:217693
Mgi Id  MGI:5615329 Doi  10.1038/ncb3058
Citation  Scheeren FA, et al. (2014) A cell-intrinsic role for TLR2-MYD88 in intestinal and breast epithelia and oncogenesis. Nat Cell Biol 16(12):1238-48
abstractText  It has been postulated that there is a link between inflammation and cancer. Here we describe a role for cell-intrinsic toll-like receptor-2 (TLR2; which is involved in inflammatory response) signalling in normal intestinal and mammary epithelial cells and oncogenesis. The downstream effectors of TLR2 are expressed by normal intestinal and mammary epithelia, including the stem/progenitor cells. Deletion of MYD88 or TLR2 in the intestinal epithelium markedly reduces DSS-induced colitis regeneration and spontaneous tumour development in mice. Limiting dilution transplantations of breast epithelial cells devoid of TLR2 or MYD88 revealed a significant decrease in mammary repopulating unit frequency compared with the control. Inhibition of TLR2, its co-receptor CD14, or its downstream targets MYD88 and IRAK1 inhibits growth of human breast cancers in vitro and in vivo. These results suggest that inhibitors of the TLR2 pathway merit investigation as possible therapeutic and chemoprevention agents.
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