S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway
Copyright policy )S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway
AbstractThe complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity against various cells, especially tumor cells. Here, we present evidence that S100A8/A9 also has cell growth-promoting activity at low concentrations. Receptor of advanced glycation end product (RAGE) gene silencing and cotreatment with a RAGE-specific blocking antibody revealed that this activity was mediated via RAGE ligation. To investigate the signaling pathways, MAPK phosphorylation and NF-κB activation were characterized in S100A8/A9-treated cells. S100A8/A9 caused a significant increase in p38 MAPK and p44/42 kinase phosphorylation, and the status of stress-activated protein kinase/JNK phosphorylation remained unchanged. Treatment of cells with S100A8/A9 also enhanced NF-κB activation. RAGE small interfering RNA pretreatment abrogated the S100A8/A9-induced NF-κB activation. Our data indicate that S100A8/A9-promoted cell growth occurs through RAGE signaling and activation of NF-κB.
- University of Manitoba Canada
- Zahedan University of Medical Sciences Iran (Islamic Republic of)
- Vanderbilt University United States
- VANDERBILT UNIVERSITY
- Linköping University Sweden
Cancer och onkologi, Molekylärbiologi, Cellbiologi, MAP Kinase Signaling System, Receptor for Advanced Glycation End Products, NF-κB proliferation MRP8 MRP14 endokines S100/calgranulins cytotoxic peptides, NF-kappa B, Cell Biology, Biochemistry, Cancer and Oncology, Cell Line, Tumor, Calgranulin B, Humans, Calgranulin A, Female, HMGB1 Protein, Phosphorylation, Receptors, Immunologic, Extracellular Signal-Regulated MAP Kinases, Biokemi, Molecular Biology, Cell Proliferation
Cancer och onkologi, Molekylärbiologi, Cellbiologi, MAP Kinase Signaling System, Receptor for Advanced Glycation End Products, NF-κB proliferation MRP8 MRP14 endokines S100/calgranulins cytotoxic peptides, NF-kappa B, Cell Biology, Biochemistry, Cancer and Oncology, Cell Line, Tumor, Calgranulin B, Humans, Calgranulin A, Female, HMGB1 Protein, Phosphorylation, Receptors, Immunologic, Extracellular Signal-Regulated MAP Kinases, Biokemi, Molecular Biology, Cell Proliferation
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