| Literature DB >> 25362351 |
Ferenc A Scheeren1, Angera H Kuo2, Linda J van Weele2, Shang Cai2, Iris Glykofridis3, Shaheen S Sikandar2, Maider Zabala2, Dalong Qian2, Jessica S Lam2, Darius Johnston2, Jens P Volkmer2, Debashis Sahoo2, Matt van de Rijn4, Frederick M Dirbas5, George Somlo6, Tomer Kalisky7, Michael E Rothenberg2, Stephen R Quake7, Michael F Clarke8.
Abstract
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.Entities:
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Year: 2014 PMID： 25362351 DOI： 10.1038/ncb3058
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824