Activation of CD47 receptors causes proliferation of human astrocytoma but not normal astrocytes via an Akt-dependent pathway
| Autor: | Thérèse B. Deramaudt, Bernard Bucher, Emilie Sick, Philippe Rondé, Philippe André, Abdelaziz Boukhari, Jean-Pierre Gies, Kenneth Takeda |
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| Rok vydání: | 2010 |
| Předmět: |
Cell type
Time Factors Apoptosis CD47 Antigen Astrocytoma Biology Tritium Antibodies Cellular and Molecular Neuroscience Cell surface receptor Autophagy Cyclic AMP medicine Humans Immunoprecipitation RNA Messenger Enzyme Inhibitors Receptor neoplasms Protein kinase B Cells Cultured PI3K/AKT/mTOR pathway Cell Proliferation Cell growth CD47 medicine.disease nervous system diseases Cell biology Oncogene Protein v-akt Neurology Astrocytes Cancer research Calcium Signal Transduction Thymidine |
| Zdroj: | Glia. 59:308-319 |
| ISSN: | 0894-1491 |
| Popis: | CD47 is a membrane receptor that plays pivotal roles in many pathophysiological processes, including infection, inflammation, cell spreading, proliferation, and apoptosis. We show that activation of CD47 increases proliferation of human U87 and U373 astrocytoma cells but not normal astrocytes. CD47 function-blocking antibodies inhibit proliferation of untreated U87 and U373 cells but not normal astrocytes, suggesting that CD47 may be constitutively activated in astrocytoma. CD47 expression levels were similar in our three cell types. CD47 couples to G-proteins in astrocytes and astrocytoma and especially to the Gβγ dimer. Downstream signaling following CD47 activation involves Gβγ dimer-dependent activation of the PI3K/Akt pathway in astrocytoma cells but not in normal astrocytes. This pathway is known to be deregulated in astrocytoma, leading to cell proliferation and enhanced survival signals. Putative PLIC-1 interaction with CD47 in astrocytoma cells but not astrocytes may contribute to the proliferative effect observed upon activation of CD47. Our data indicate that CD47 receptors have a stimulatory role in cell proliferation and demonstrate for the first time that CD47 signals via the PI3K/Akt pathway in cancerous cells but not normal cells. |
| Databáze: | OpenAIRE |
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