title: Aurora kinase A is a target of Wnt/beta-catenin involved in multiple myeloma disease progression.
abstract: 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.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors: Jui
authors: J
authors: Dutta-Simmons
authors: Yunyu
authors: Y
authors: Zhang
authors: Gullu
authors: G
authors: Gorgun
authors: Moshe
authors: M
authors: Gatt
authors: Mala
authors: M
authors: Mani
authors: Teru
authors: T
authors: Hideshima
authors: Kohichi
authors: K
authors: Takada
authors: Nicole E
authors: NE
authors: Carlson
authors: Daniel E
authors: DE
authors: Carrasco
authors: Yu-Tzu
authors: YT
authors: Tai
authors: Noopur
authors: N
authors: Raje
authors: Anthony G
authors: AG
authors: Letai
authors: Kenneth C
authors: KC
authors: Anderson
authors: Daniel R
authors: DR
authors: Carrasco
mesh_terms: D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; C576917:AURKA protein, human; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases