Aurora kinase A is a target of Wnt/beta-catenin involved in multiple myeloma disease progression.
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.
Dutta-Simmons
Jui
J
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Zhang
Yunyu
Y
Gorgun
Gullu
G
Gatt
Moshe
M
Mani
Mala
M
Hideshima
Teru
T
Takada
Kohichi
K
Carlson
Nicole E
NE
Carrasco
Daniel E
DE
Tai
Yu-Tzu
YT
Raje
Noopur
N
Letai
Anthony G
AG
Anderson
Kenneth C
KC
Carrasco
Daniel R
DR
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*
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