Print Email Facebook Twitter Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression 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 LifeMHR - Metabolic Health ResearchELSS - Earth, Life and Social SciencesBiomedical InnovationBiologyHealthy LivingC-reactive proteinInvasionMMP-9S1P2 (2 amino 3 methoxyphenyl)chromoneC reactive proteinCCAAT enhancer binding protein betaFingolimodGelatinase BMitogen activated protein kinase kinaseReactive oxygen metaboliteSphingosine 1 phosphateAnimal experimentAnimal modelBreast carcinomaBreast cellCancer growthCell invasionControlled studyEnzyme activationEpithelium cellFemaleHumanHuman cellIn vitro studyIn vivo studyInflammationInflammatory breast cancerMouseNonhumanOncogene c fosPhenotypePriority journalProtein expressionTranscription initiationTumor invasionUpregulationXenograftMus 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 Files To receive the publication files, please send an e-mail request to TNO Library.