NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases
| Autor: | Mamatha M. Reddy, James D. Griffin, Ross L. Levine, Margret S. Fernandes, Martin Sattler, Ravi Salgia |
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| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Myeloid migration Article Cell Line Myeloid neoplasia Mice 03 medical and health sciences 0302 clinical medicine Cell Movement hemic and lymphatic diseases medicine Animals Humans Myeloid Cells MARCKS tyrosine kinase oncogene Cell Proliferation 030304 developmental biology 0303 health sciences NADPH oxidase biology NADPH Oxidases NOX4 Myeloid leukemia Oncogenes Hematology Protein-Tyrosine Kinases Cell Transformation Neoplastic medicine.anatomical_structure Oncology Leukemia Myeloid 030220 oncology & carcinogenesis cardiovascular system biology.protein Cancer research Phosphorylation Signal transduction Tyrosine kinase NADP signal transduction |
| Zdroj: | Leukemia |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/leu.2010.263 |
| Popis: | Transformation by tyrosine kinase oncogenes (TKOs) in myeloid malignancies, including BCR-ABL in chronic myeloid leukemia, FLT3ITD in acute myeloid leukemia or JAK2V617F in myeloproliferative neoplasms, is associated with increased growth and cytoskeletal abnormalities. Using targeted approaches against components of the superoxide-producing NADPH-oxidases, including NADPH oxidase 2 (NOX2), NOX4 and the common p22(phox) subunit of NOX1-4, myeloid cells were found to display reduced cell growth and spontaneous migration. Consistent with a role of NOXs as regulators of membrane proximal signaling events in nonphagocytic cells, NOX2 and NOX4 were not involved in the excess production of intracellular reactive oxygen species and did not significantly increase oxygen consumption. All NOX family members are controlled in part through levels of the rate-limiting substrate NADPH, which was found to be significantly elevated in TKO-transformed cells. Also, reduced phosphorylation of the actin filament crosslinking protein myristoylated alanine-rich C-kinase substrate (MARCKS) in response to suppression of p22(phox) hints at a novel effector of NOX signaling. MARCKS was also found to be required for increased migration. Overall, these data suggest a model whereby NOX links metabolic NADPH production to cellular events that directly contribute to transformation. |
| Databáze: | OpenAIRE |
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