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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Windischhofer, W; Huber, E; Rossmann, C; Semlitsch, M; Kitz, K; Rauh, A; Devaney, T; Leis, HJ; Malle, E.
LPA-induced suppression of periostin in human osteosarcoma cells is mediated by the LPA(1)/Egr-1 axis.
Biochimie. 2012; 94(9):1997-2005
Doi: 10.1016/j.biochi.2012.05.023
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Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Windischhofer Werner
- Co-Autor*innen der Med Uni Graz
- DeVaney Trevor
- Huber Evelyn
- Kitz Kerstin
- Leis Hans-Joerg
- Malle Ernst
- Rauh Anamaria
- Rossmann Christine Renate
- Semlitsch Michaela
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- Abstract:
- Lysophosphatidic acid (LPA), a naturally occurring bioactive phospholipid, mediates a multitude of (patho)physiological events including activation of mitogen-activated protein kinases (MAPKs). As LPA may induce cellular reponses in human osteosarcoma, the present study aimed at investigating expression of various LPA receptors, LPA-mediated activation of MAPK via G-protein coupling, and expression of early response genes in a cellular model for human osteosarcoma. We show that MG-63 cells express three members of the endothelial differentiation gene (Edg) family of G-protein coupled receptor transcripts (LPA(1-3)) but only two (LPA(4/5)) out of three members of the non-Edg family LPA receptor transcripts. Stimulation of MG-63 cells with LPA or synthetic LPA receptor agonists resulted in p42/44 MAPK phosphorylation via LPA(1)-LPA(3) receptors. Using pharmacological inhibitors, we show that LPA-mediated phosphorylation of p42/44 MAPK by LPA receptor engagement is transmitted by G(αi)-dependent pathways through the Src family of tyrosine kinases. As a consequence, a rapid and transient upregulation of the zinc finger transcription factor early growth response-1 (Egr-1) was observed. Egr-1 expression was strictly mediated via G(αi)/Src/p42/44 MAPK pathway; no involvement of the G(αq/11)/PLC/PKC or the PLD/PI3 kinase/Akt pathways was found. LPA-induced expression of functional Egr-1 in MG-63 cells could be confirmed by electrophoretic mobility shift assay. LPA-induced Egr-1 upregulation was accompanied by a time-dependent decrease of periostin (previously called osteoblast-specific factor 2), a cell adhesion protein for pre-osteoblasts. Silencing of LPA(1) and/or Egr-1 in MG-63 cells reversed LPA-mediated suppression of periostin. We here demonstrate a crosslink between Egr-1 and periostin in cancer cells, in particular in human osteosarcoma. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Cell Adhesion Molecules - metabolism
- Cell Line, Tumor -
- Cell Proliferation - drug effects
- DNA - metabolism
- Early Growth Response Protein 1 - biosynthesis
- Early Growth Response Protein 1 - genetics
- Early Growth Response Protein 1 - metabolism
- GTP-Binding Protein alpha Subunits, Gi-Go - metabolism
- Gene Expression Regulation, Neoplastic - drug effects
- Humans -
- Lysophospholipids - pharmacology
- MAP Kinase Signaling System - drug effects
- Mitogen-Activated Protein Kinase 1 - metabolism
- Mitogen-Activated Protein Kinase 3 - metabolism
- Osteosarcoma - pathology
- RNA, Messenger - genetics
- RNA, Messenger - metabolism
- Receptors, Lysophosphatidic Acid - metabolism
- Find related publications in this database (Keywords)
- LPA
- EGF receptor
- Egr-1
- Bone
- Periostin
- MAPK