Aurora kinase A is a target of Wnt/β-catenin involved in multiple myeloma disease progression
| Autor: | Daniel R. Carrasco, Yunyu Zhang, Moshe E. Gatt, Kohichi Takada, Gullu Gorgun, Anthony Letai, Teru Hideshima, Jui Dutta-Simmons, Kenneth C. Anderson, Mala Mani, Noopur Raje, Daniel E. Carrasco, Nicole Carlson, Yu-Tzu Tai |
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| Rok vydání: | 2009 |
| Předmět: |
Transplantation
Heterologous Immunology Aurora inhibitor Mice Transgenic Mice SCID Protein Serine-Threonine Kinases Biology Biochemistry Gene Expression Regulation Enzymologic Mice Aurora kinase Aurora Kinases Mice Inbred NOD Tumor Cells Cultured medicine Animals Humans beta Catenin Multiple myeloma Aurora Kinase A Cell Proliferation Cell Cycle Wnt signaling pathway Cancer Cell Biology Hematology medicine.disease Gene Expression Regulation Neoplastic Wnt Proteins Drug Resistance Neoplasm Catenin Disease Progression Cancer research Multiple Myeloma Monoclonal gammopathy of undetermined significance |
| Zdroj: | Blood. 114:2699-2708 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Multiple myeloma (MM) is a cancer of plasma cells with complex molecular characteristics that evolves from monoclonal gammopathy of undetermined significance, a highly prevalent premalignant condition. MM is the second most frequent hematologic cancer in the United States, and it remains incurable, thereby highlighting the need for new therapeutic approaches, particularly those targeting common molecular pathways involved in disease progression and maintenance, shared across different MM subtypes. Here we report that Wnt/β-catenin is one such pathway. We document the involvement of β-catenin in cell-cycle regulation, proliferation, and invasion contributing to enhanced proliferative and metastatic properties of MM. The pleiotropic effects of β-catenin in MM correlate with its transcriptional function, and we demonstrate regulation of a novel target gene, Aurora kinase A, implicating β-catenin in G2/M regulation. β-catenin and Aurora kinase A are present in most MM but not in normal plasma cells and are expressed in a pattern that parallels progression from monoclonal gammopathy of undetermined significance to MM. Our data provide evidence for a novel functional link between β-catenin and Aurora kinase A, underscoring a critical role of these pathways in MM disease progression. |
| Databáze: | OpenAIRE |
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