Novel molecular mechanisms by inorganic phosphate in osteosarcoma U2OS cells
| Autor: | Raffaella D'Auria, Emilio Chiosi, G. Illiano, Borrelli, Annamaria Spina, Silvio Naviglio, Di Gesto D, A. Sorrentino, F. Illiano, Forni M |
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| Přispěvatelé: | Naviglio, Silvio, Di GESTO, D, Borrelli, V, Forni, M, Illiano, F, D'Auria, R, Sorrentino, A, Chiosi, Emilio, Illiano, G, Spina, Annamaria |
| Rok vydání: | 2009 |
| Předmět: |
Osteosarcoma
biology General Immunology and Microbiology Chemistry Cell growth Integrin medicine.disease General Biochemistry Genetics and Molecular Biology Cell biology Phosphates Inorganic Phosphate cAMP Rap1 ERK1/2 integrins Osteosarcoma Cell culture Cell Line Tumor medicine biology.protein Cell Adhesion Phosphorylation Humans Rap1 Signal transduction Cell adhesion Cell Proliferation |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1945-0508 1945-0494 |
| DOI: | 10.2741/328 |
| Popis: | "Osteosarcoma is the most common malignant. primary bone tumor in children and adolescents and is. characterized by a high metastatic potential. Its clinical. outcome remains discouraging despite aggressive. treatments. Thus, novel therapeutic approaches are needed.. Recent results indicate that inorganic phosphate (Pi) is. capable of affecting specific signal transduction pathways. and of acting as an active regulator of cell behaviour.. Previously, we found that Pi inhibits proliferation of human. osteosarcoma U2OS cells via an adenylate cyclase/cAMP. mediated mechanism. Here, we report that upon Pi. treatment, U2OS cells become extremely hard to dislodge. with trypsin. The lack of sensitivity to the trypsin action. was paralleled by relevant changes in integrin subunits. expression and accompanied by an increase of cell. adhesion in cell-matrix adhesion assays. Interestingly,. exposure of U2OS cells to Pi results also in a strong. activation and protein level up-regulation of Rap1 small. GTPase and in an early increase followed by a sustained. inhibition of Erk1/2 phosphorylation. Importantly, the Piinduced. increase of cell adhesion was enforced by a cAMP. analogue which specifically activated Epac/Rap1 and. insensitive to PKA and MEK1/2 inhibitors. Our results. enforce the evidences of inorganic phosphate as a. signalling molecule, identify beta3 integrin, Rap1, ERK1/2. as proteins whose expression and function are relevantly. affected by Pi in osteosarcoma U2OS cells The clinical. significance and potential therapeutic applications by our. data will be discussed." |
| Databáze: | OpenAIRE |
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