PMID- 25691060
OWN - NLM
STAT- MEDLINE
DCOM- 20160303
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 8
DP  - 2015 Mar 20
TI  - Myeloid differentiation primary response gene 88-leukotriene B4 receptor 2 
      cascade mediates lipopolysaccharide-potentiated invasiveness of breast cancer 
      cells.
PG  - 5749-59
AB  - 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 B4 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-kappaB 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.
FAU - Park, Geun-Soo
AU  - Park GS
AD  - College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
FAU - Kim, Jae-Hong
AU  - Kim JH
AD  - College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (LTB4R2 protein, human)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Receptors, Leukotriene B4)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/genetics/metabolism/*pathology
MH  - Cell Differentiation/physiology
MH  - Cell Line, Tumor
MH  - Female
MH  - Heterografts
MH  - Humans
MH  - Interleukin-6/biosynthesis/genetics
MH  - Interleukin-8/biosynthesis/genetics
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Myeloid Cells/pathology
MH  - Myeloid Differentiation Factor 88/genetics/*metabolism
MH  - Neoplasm Invasiveness
MH  - Receptors, Leukotriene B4/*biosynthesis/genetics
MH  - Signal Transduction
MH  - Transcriptional Activation
MH  - Transfection
MH  - Up-Regulation
PMC - PMC4467399
OTO - NOTNLM
OT  - BLT2
OT  - IL-6/IL-8
OT  - LPS
OT  - MyD88
OT  - invasiveness
EDAT- 2015/02/19 06:00
MHDA- 2016/03/05 06:00
PMCR- 2015/03/20
CRDT- 2015/02/19 06:00
PHST- 2014/12/03 00:00 [received]
PHST- 2015/01/02 00:00 [accepted]
PHST- 2015/02/19 06:00 [entrez]
PHST- 2015/02/19 06:00 [pubmed]
PHST- 2016/03/05 06:00 [medline]
PHST- 2015/03/20 00:00 [pmc-release]
AID - 3304 [pii]
AID - 10.18632/oncotarget.3304 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Mar 20;6(8):5749-59. doi: 10.18632/oncotarget.3304.