Title
Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression
Author
Kim, E.S.
Cha, Y.
Ham, M.
Jung, J.
Kim, S.G.
Hwang, S.
Kleemann, R.
Moon, A.
Publication year
2014
Abstract
A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for the expression of CRP and its functional significance in breast cell invasion. The present study aimed to elucidate the molecular link between S1P and CRP during the invasive process of breast epithelial cells. This is the first report showing that transcription of CRP was markedly activated by S1P in breast cells. Our data suggest that not only S1P treatment but also the endogenously produced S1P may upregulate CRP in breast carcinoma cells. Transcription factors CCAAT/enhancer-binding protein beta and c-fos were required for S1P-induced CRP expression. Coupling of S1P 3 to heterotrimeric G q triggered the expression of CRP, utilizing signaling pathways involving reactive oxygen species (ROS), Ca 2+ and extracellular signal-related kinases (ERKs). S1P-induced CRP expression was crucial for the transcriptional activation of matrix metalloproteinase-9 through ERKs, ROS and c-fos, leading to breast cell invasion. Using a xenograft mice tumor model, we demonstrated that S1P induced CRP expression both in vitro and in vivo. Taken together, our findings have revealed a molecular basis for S1P-induced transcriptional activation of CRP and its functional significance in the acquisition of the invasive phenotype of human breast epithelial cells under inflammatory conditions. Our findings may provide useful information on the identification of useful therapeutic targets for inflammatory breast cancer. © 2014 Macmillan Publishers Limited. Chemicals/CAS: 2 (2 amino 3 methoxyphenyl)chromone, 167869-21-8; C reactive protein, 9007-41-4; fingolimod, 162359-56-0; gelatinase B, 146480-36-6; mitogen activated protein kinase kinase, 142805-58-1; sphingosine 1 phosphate, 26993-30-6. Tradenames: pd 98059.
Subject
Life
MHR - Metabolic Health Research
ELSS - Earth, Life and Social Sciences
Biomedical Innovation
Biology
Healthy Living
C-reactive protein
Invasion
MMP-9
S1P
2 (2 amino 3 methoxyphenyl)chromone
C reactive protein
CCAAT enhancer binding protein beta
Fingolimod
Gelatinase B
Mitogen activated protein kinase kinase
Reactive oxygen metabolite
Sphingosine 1 phosphate
Animal experiment
Animal model
Breast carcinoma
Breast cell
Cancer growth
Cell invasion
Controlled study
Enzyme activation
Epithelium cell
Female
Human
Human cell
In vitro study
In vivo study
Inflammation
Inflammatory breast cancer
Mouse
Nonhuman
Oncogene c fos
Phenotype
Priority journal
Protein expression
Transcription initiation
Tumor invasion
Upregulation
Xenograft
Mus
To reference this document use:
http://resolver.tudelft.nl/uuid:250aaa1d-edef-41e5-9c09-5af403b72229
DOI
https://doi.org/10.1038/onc.2013.319
TNO identifier
513443
ISSN
1476-5594
Source
Oncogene, 33 (27), 3583-3593
Document type
article