Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms9746
Title: IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel
Authors: Wee, Z.N
Yatim, S.M.J.M
Kohlbauer, V.K
Feng, M
Goh, J.Y
Yi, B
Lee, P.L
Zhang, S 
Wang, P.P
Lim, E
Tam, W.L 
Cai, Y
Ditzel, H.J
Hoon, D.S.B
Tan, E.Y
Yu, Q 
Keywords: apoptosis
cancer
gene expression
hormone
rabies
secretion
tumor
antineoplastic agent
interleukin 1 receptor associated kinase
IRAK1 protein, human
paclitaxel
animal
antagonists and inhibitors
apoptosis
Breast Neoplasms
cell proliferation
drug effects
drug resistance
enzymology
female
genetics
human
metabolism
metastasis
mouse
pathology
phosphorylation
SCID mouse
tumor cell line
Animals
Antineoplastic Agents, Phytogenic
Apoptosis
Breast Neoplasms
Cell Line, Tumor
Cell Proliferation
Drug Resistance, Neoplasm
Female
Humans
Interleukin-1 Receptor-Associated Kinases
Mice
Mice, SCID
Neoplasm Metastasis
Paclitaxel
Phosphorylation
Issue Date: 2015
Publisher: Nature Publishing Group
Citation: Wee, Z.N, Yatim, S.M.J.M, Kohlbauer, V.K, Feng, M, Goh, J.Y, Yi, B, Lee, P.L, Zhang, S, Wang, P.P, Lim, E, Tam, W.L, Cai, Y, Ditzel, H.J, Hoon, D.S.B, Tan, E.Y, Yu, Q (2015). IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel. Nature Communications 6 : 8746. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms9746
Rights: Attribution 4.0 International
Abstract: Metastatic tumour recurrence due to failed treatments remains a major challenge of breast cancer clinical management. Here we report that interleukin-1 receptor-associated kinase 1 (IRAK1) is overexpressed in a subset of breast cancers, in particular triple-negative breast cancer (TNBC), where it acts to drive aggressive growth, metastasis and acquired resistance to paclitaxel treatment. We show that IRAK1 overexpression confers TNBC growth advantage through NF-B-related cytokine secretion and metastatic TNBC cells exhibit gain of IRAK1 dependency, resulting in high susceptibility to genetic and pharmacologic inhibition of IRAK1. Importantly, paclitaxel treatment induces strong IRAK1 phosphorylation, an increase in inflammatory cytokine expression, enrichment of cancer stem cells and acquired resistance to paclitaxel treatment. Pharmacologic inhibition of IRAK1 is able to reverse paclitaxel resistance by triggering massive apoptosis at least in part through inhibiting p38-MCL1 pro-survival pathway. Our study thus demonstrates IRAK1 as a promising therapeutic target for TNBC metastasis and paclitaxel resistance. © 2015 Macmillan Publishers Limited. All rights reserved.
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/180422
ISSN: 2041-1723
DOI: 10.1038/ncomms9746
Rights: Attribution 4.0 International
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