Wnts induce migration and invasion of myeloma plasma cells.
Multiple myeloma is an incurable form of lymphoid cancer characterized by accumulation of neoplastic plasma cells in the bone marrow cavity. Little is known about the mechanisms regulating myeloma cell movement within the bone marrow and metastasis to secondary sites. Herein, we identify multiple members of the wingless/int (Wnt) family as promoters of myeloma cell migration/invasion. Wnt-mediated migration was associated with the Wnt/RhoA pathway and did not necessitate signaling through beta-catenin. Activation of both RhoA and members of the protein kinase C (PKC) family, including PKCalpha, PKCbeta, and PKCmu, were required for induction of migration. Activated RhoA and PKCalpha, PKCbeta, and PKCmu appear to assemble in macromolecular signaling complexes that are associated with the cell membrane. These results suggest that Wnt responsiveness of myeloma plasma cells may be a significant factor in disease progression.
Qiang
Ya-Wei
YW
Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
Walsh
Katie
K
Yao
Lei
L
Kedei
Noemi
N
Blumberg
Peter M
PM
Rubin
Jeffrey S
JS
Shaughnessy
John
J
Rudikoff
Stuart
S
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology* / Q000502:physiology; D046911:Macromolecular Substances / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051153:Wnt Proteins; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D051153:Wnt Proteins; D011493:Protein Kinase C; D020742:rhoA GTP-Binding Protein