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Myeloid differentiation primary response gene 88-leukotriene B4 receptor 2 cascade mediates lipopolysaccharide-potentiated invasiveness of breast cancer cells

Authors
Park, Geun-SooKim, Jae-Hong
Issue Date
20-3월-2015
Publisher
IMPACT JOURNALS LLC
Keywords
LPS; MyD88; Invasiveness; BLT2; IL-6/IL-8
Citation
ONCOTARGET, v.6, no.8, pp.5749 - 5759
Indexed
SCIE
SCOPUS
Journal Title
ONCOTARGET
Volume
6
Number
8
Start Page
5749
End Page
5759
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/94103
DOI
10.18632/oncotarget.3304
ISSN
1949-2553
Abstract
Inflammation and local inflammatory mediators are inextricably linked to tumor progression through complex pathways in the tumor microenvironment. Lipopolysaccharide (LPS) exposure to tumor cells has been suggested to promote tumor invasiveness and metastasis. However, the detailed signaling mechanism involved has not been elucidated. In this study, we showed that LPS upregulated the expression of leukotriene B-4 receptor-2 (BLT2) and the synthesis of BLT2 ligands in MDA-MB-231 and MDA-MB-435 breast cancer cells, thereby promoting invasiveness. BLT2 depletion with siRNA clearly attenuated LPS-induced invasiveness. In addition, we demonstrated that myeloid differentiation primary response gene 88 (MyD88) lies upstream of BLT2 in LPS-potentiated invasiveness and that this 'MyD88-BLT2' cascade mediates activation of NF-kappa B and the synthesis of IL-6 and IL-8, which are critical for the invasiveness and aggression of breast cancer cells. LPS-driven metastasis of MDA-MB-231 cells was also markedly suppressed by the inhibition of BLT2. Together, our results demonstrate, for the first time, that LPS potentiates the invasiveness and metastasis of breast cancer cells via a 'MyD88-BLT2'-linked signaling cascade.
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Kim, Jae Hong
생명과학대학 (생명과학부)
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