极光激酶A是参与多发性骨髓瘤疾病进展的Wnt/β-连环蛋白的一个靶点。
Aurora kinase A is a target of Wnt/beta-catenin involved in multiple myeloma disease progression.
作者信息
Dutta-Simmons Jui, Zhang Yunyu, Gorgun Gullu, Gatt Moshe, Mani Mala, Hideshima Teru, Takada Kohichi, Carlson Nicole E, Carrasco Daniel E, Tai Yu-Tzu, Raje Noopur, Letai Anthony G, Anderson Kenneth C, Carrasco Daniel R
机构信息
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Blood. 2009 Sep 24;114(13):2699-708. doi: 10.1182/blood-2008-12-194290. Epub 2009 Aug 3.
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/beta-catenin is one such pathway. We document the involvement of beta-catenin in cell-cycle regulation, proliferation, and invasion contributing to enhanced proliferative and metastatic properties of MM. The pleiotropic effects of beta-catenin in MM correlate with its transcriptional function, and we demonstrate regulation of a novel target gene, Aurora kinase A, implicating beta-catenin in G2/M regulation. beta-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 beta-catenin and Aurora kinase A, underscoring a critical role of these pathways in MM disease progression.
多发性骨髓瘤(MM)是一种浆细胞癌,具有复杂的分子特征,由意义未明的单克隆丙种球蛋白病演变而来,这是一种高度普遍的癌前病变。MM是美国第二常见的血液系统癌症,且仍然无法治愈,因此凸显了对新治疗方法的需求,特别是那些针对不同MM亚型中共同参与疾病进展和维持的分子途径的方法。在此我们报告Wnt/β-连环蛋白就是这样一种途径。我们证明β-连环蛋白参与细胞周期调控、增殖和侵袭,有助于增强MM的增殖和转移特性。β-连环蛋白在MM中的多效性作用与其转录功能相关,并且我们证明了一个新的靶基因Aurora激酶A的调控,这表明β-连环蛋白参与G2/M调控。β-连环蛋白和Aurora激酶A存在于大多数MM中,但不存在于正常浆细胞中,并且其表达模式与从意义未明的单克隆丙种球蛋白病进展到MM的过程平行。我们的数据为β-连环蛋白和Aurora激酶A之间的新型功能联系提供了证据,强调了这些途径在MM疾病进展中的关键作用。