Wnt signaling in B-cell neoplasia

• Published in: Oncogene Vol. 22; no. 10; pp. 1536 - 1545
• Main Authors: QIANG, Ya-Wei, ENDO, Yoshimi, RUBIN, Jeffrey S, RUDIKOFF, Stuart
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 13.03.2003; Nature Publishing Group
• Subjects: Actin; Actins - drug effects; Actins - metabolism; Actins - ultrastructure; Adaptor Proteins, Signal Transducing; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; beta Catenin; Biological and medical sciences; Cancer; Cell culture; Cell cycle; Cell differentiation; Cell Lineage; Cellular signal transduction; Cytokines; Cytoskeletal Proteins - metabolism; Cytoskeleton; Diagnosis; Dishevelled Proteins; DNA-Binding Proteins - metabolism; Frizzled protein; Frizzled Receptors; Fundamental and applied biological sciences. Psychology; Genetic aspects; Glycoproteins - secretion; Growth factors; Health aspects; Humans; Intercellular Signaling Peptides and Proteins; LDL-Receptor Related Proteins; Low density lipoprotein; Low Density Lipoprotein Receptor-Related Protein-5; Low Density Lipoprotein Receptor-Related Protein-6; Low density lipoprotein receptors; LRP5 protein; Lymphocytes B; Lymphoma; Lymphoma, B-Cell - drug therapy; Lymphoma, B-Cell - metabolism; Metastases; Molecular and cellular biology; Morphology; Multiple myeloma; Multiple Myeloma - metabolism; Mutation; Non-Hodgkin's lymphomas; Phosphoproteins; Phosphorylation; Plasma cells; Proteins; Proteins - drug effects; Proteins - metabolism; Proteins - pharmacology; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, G-Protein-Coupled; Receptors, LDL - genetics; Receptors, LDL - metabolism; rhoA GTP-Binding Protein - metabolism; Roles; Saccharomyces cerevisiae Proteins; Signal Transduction; Trans-Activators - metabolism; Transcription factors; Tumors; Wnt protein; Wnt Proteins; Wnt3 Protein; Wnt3A Protein; β-Catenin; United States; United States > US; Rho; β-catenin; Genetics; myeloma; morphology; Wnt
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1206239

Wnts comprise a family of secreted proteins that interact with receptors consisting of a Frizzled (Fz) family member alone or complexed with LDL receptor-related proteins (LRP5/6). Wnt signaling plays a crucial role in both development and differentiation, and activation of a 'canonical' Wnt pathway resulting in beta-catenin stabilization is associated with several types of human cancers. To date, little is known about potential Wnt signaling in mature lymphocytes or lymphoid neoplasia. Herein, we have analysed Wnt signaling in mature B cells (lymphomas) and plasma cells (multiple myeloma). Both Fz and LRP5/6 mRNAs were expressed in myeloma lines, but LRP5/6 were not observed in lymphomas. In myelomas, a canonical Wnt signaling pathway was activated following treatment with Wnt-3a as assessed by accumulation of beta-catenin, but beta-catenin levels actually decreased in lymphoma cells. Wnt-3a treatment further led to striking morphological changes in myeloma cells accompanied by rearrangement of the actin cytoskeleton. Morphological changes were associated with a second Wnt pathway dependent on Rho activation. These results suggest that Wnt responsiveness is a stage-specific phenomenon in B-cell development and that the morphological changes associated with Wnt signaling may play a role in the motility and metastatic potential of myeloma cells.