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Nat Cell Biol. 2014 Dec;16(12):1238-48. doi: 10.1038/ncb3058. Epub 2014 Nov 2.

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

Author information

1
1] Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 265 Campus Drive Stanford, California 94305, USA [2] The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
2
Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 265 Campus Drive Stanford, California 94305, USA.
3
The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
4
Department of Pathology, Stanford University, Stanford, California 94305, USA.
5
Department of Surgery, Stanford University, Stanford, California 94305, USA.
6
Department of Medical Oncology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
7
Department of Bioengineering and Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
8
1] Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, 265 Campus Drive Stanford, California 94305, USA [2] Department of medicine, Division of Oncology, Stanford University, Stanford, California 94305, USA.

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.

PMID:
25362351
DOI:
10.1038/ncb3058
[Indexed for MEDLINE]

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