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

作者：Scheeren Ferenc A; Kuo Angera H; van Weele Linda J; Cai Shang; Glykofridis Iris; Sikandar Shaheen S; Zabala Maider; Qian Dalong; Lam Jessica S; Johnston Darius; Volkmer Jens P; Sahoo Debashis; van de Rijn Matt; Dirbas Frederick M; Somlo George; Kalisky Tomer; Rothenberg Michael E; Quake Stephen R; Clarke Michael F^*

来源：Nature Cell Biology, 2014, 16(12): 1238-U245.

DOI：10.1038/ncb3058

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 CD 14, 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.

• 出版日期2014-12