Toll-Like Receptors and Cancer: MYD88 Mutation and Inflammation

Pattern recognition receptors (PRRs) expressed on immune cells are crucial for the early detection of invading pathogens, in initiating early innate immune response and in orchestrating the adaptive immune response. PRRs are activated by specific pathogen-associated molecular patterns that are prese...

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Main Authors:	Wang, James Q., Jeelall, Yogesh S., Ferguson, Laura L., Horikawa, Keisuke
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116802/

id	pubmed-4116802
recordtype	oai_dc
spelling	pubmed-41168022014-08-15 Toll-Like Receptors and Cancer: MYD88 Mutation and Inflammation Wang, James Q. Jeelall, Yogesh S. Ferguson, Laura L. Horikawa, Keisuke Immunology Pattern recognition receptors (PRRs) expressed on immune cells are crucial for the early detection of invading pathogens, in initiating early innate immune response and in orchestrating the adaptive immune response. PRRs are activated by specific pathogen-associated molecular patterns that are present in pathogenic microbes or nucleic acids of viruses or bacteria. However, inappropriate activation of these PRRs, such as the Toll-like receptors (TLRs), due to genetic lesions or chronic inflammation has been demonstrated to be a major cause of many hematological malignancies. Gain-of-function mutations in the TLR adaptor protein MYD88 found in 39% of the activated B cell type of diffuse large B cell lymphomas and almost 100% of Waldenström’s macroglobulinemia further highlight the involvement of TLRs in these malignancies. MYD88 mutations result in the chronic activation of TLR signaling pathways, thus the constitutive activation of the transcription factor NFκB to promote cell survival and proliferation. These recent insights into TLR pathway driven malignancies warrant the need for a better understanding of TLRs in cancers and the development of novel anti-cancer therapies targeting TLRs. This review focuses on TLR function and signaling in normal or inflammatory conditions, and how mutations can hijack the TLR signaling pathways to give rise to cancer. Finally, we discuss how potential therapeutic agents could be used to restore normal responses to TLRs and have long lasting anti-tumor effects. Frontiers Media S.A. 2014-07-31 /pmc/articles/PMC4116802/ /pubmed/25132836 http://dx.doi.org/10.3389/fimmu.2014.00367 Text en Copyright © 2014 Wang, Jeelall, Ferguson and Horikawa. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wang, James Q. Jeelall, Yogesh S. Ferguson, Laura L. Horikawa, Keisuke
spellingShingle	Wang, James Q. Jeelall, Yogesh S. Ferguson, Laura L. Horikawa, Keisuke Toll-Like Receptors and Cancer: MYD88 Mutation and Inflammation
author_facet	Wang, James Q. Jeelall, Yogesh S. Ferguson, Laura L. Horikawa, Keisuke
author_sort	Wang, James Q.
title	Toll-Like Receptors and Cancer: MYD88 Mutation and Inflammation
title_short	Toll-Like Receptors and Cancer: MYD88 Mutation and Inflammation
title_full	Toll-Like Receptors and Cancer: MYD88 Mutation and Inflammation
title_fullStr	Toll-Like Receptors and Cancer: MYD88 Mutation and Inflammation
title_full_unstemmed	Toll-Like Receptors and Cancer: MYD88 Mutation and Inflammation
title_sort	toll-like receptors and cancer: myd88 mutation and inflammation
description	Pattern recognition receptors (PRRs) expressed on immune cells are crucial for the early detection of invading pathogens, in initiating early innate immune response and in orchestrating the adaptive immune response. PRRs are activated by specific pathogen-associated molecular patterns that are present in pathogenic microbes or nucleic acids of viruses or bacteria. However, inappropriate activation of these PRRs, such as the Toll-like receptors (TLRs), due to genetic lesions or chronic inflammation has been demonstrated to be a major cause of many hematological malignancies. Gain-of-function mutations in the TLR adaptor protein MYD88 found in 39% of the activated B cell type of diffuse large B cell lymphomas and almost 100% of Waldenström’s macroglobulinemia further highlight the involvement of TLRs in these malignancies. MYD88 mutations result in the chronic activation of TLR signaling pathways, thus the constitutive activation of the transcription factor NFκB to promote cell survival and proliferation. These recent insights into TLR pathway driven malignancies warrant the need for a better understanding of TLRs in cancers and the development of novel anti-cancer therapies targeting TLRs. This review focuses on TLR function and signaling in normal or inflammatory conditions, and how mutations can hijack the TLR signaling pathways to give rise to cancer. Finally, we discuss how potential therapeutic agents could be used to restore normal responses to TLRs and have long lasting anti-tumor effects.
publisher	Frontiers Media S.A.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116802/
_version_	1613119356249571328

Toll-Like Receptors and Cancer: MYD88 Mutation and Inflammation

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