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- Bénédicte Delaval
- 1Molecular Oncology and Laboratories of
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- Sébastien Létard
- 2Molecular Hematopoiesis, Marseille Cancer Institute, UMR599 Inserm and Institut Paoli-Calmettes, Marseilles, France;
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- Hélène Lelièvre
- 1Molecular Oncology and Laboratories of
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- Véronique Chevrier
- 3U366 Inserm, Grenoble; and
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- Laurent Daviet
- 4Hybrigenics S.A., Paris, France
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- Patrice Dubreuil
- 2Molecular Hematopoiesis, Marseille Cancer Institute, UMR599 Inserm and Institut Paoli-Calmettes, Marseilles, France;
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- Daniel Birnbaum
- 1Molecular Oncology and Laboratories of
抄録
<jats:title>Abstract</jats:title> <jats:p>Myeloproliferative disorders (MPD) are malignant diseases of hematopoietic progenitor cells. Many MPDs result from a chromosomal translocation that creates a fusion gene encoding a chimeric kinase. The fibroblast growth factor receptor 1 (FGFR1)-MPD is characterized by the fusion of the FGFR1 kinase with various partners, including FOP. We show here that both normal FOP and FOP-FGFR1 fusion kinase localize to the centrosome. The fusion kinase encounters substrates at the centrosome where it induces strong phosphorylation on tyrosine residues. Treatment with FGFR1 kinase inhibitor SU5402 abolishes FOP-FGFR1-induced centrosomal phosphorylation and suppresses the proliferative and survival potentials of FOP-FGFR1 Ba/F3 cells. We further show that FOP-FGFR1 allows cells to overcome G1 arrest. Therefore, the FOP-FGFR1 fusion kinase targets the centrosome, activates signaling pathways at this organelle, and sustains continuous entry in the cell cycle. This could represent a potential new mechanism of oncogenic transformation occurring specifically at the centrosome.</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 65 (16), 7231-7240, 2005-08-15
American Association for Cancer Research (AACR)
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キーワード
詳細情報 詳細情報について
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- CRID
- 1360574093575733376
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- NII論文ID
- 30018589431
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- ISSN
- 15387445
- 00085472
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