Abstract
The expression and biologic function of the gene encoding vacuolar protein sorting 4B (VPS4B) in human multiple myeloma (MM) were investigated in this study. We determined that VPS4B expression is decreased in adherent MM cells and that knockdown of VPS4B expression induces cell adhesion-mediated drug resistance (CAM-DR) in MM. This induced CAM-DR phenotype manifested through down-regulation of cell apoptosis and requires phosphorylation of AKT and Erk. Finally, VPS4B expression was positively correlated with cell proliferation. Our findings support a role for VPS4B in MM cell proliferation, adhesion, and drug resistance, and pave the way for a novel therapeutic approach targeting this molecule.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATPases Associated with Diverse Cellular Activities
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Adenosine Triphosphatases / genetics*
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Adenosine Triphosphatases / metabolism
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Apoptosis / genetics
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Cell Adhesion / genetics
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Cell Line, Tumor
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Down-Regulation
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Drug Resistance, Neoplasm / genetics*
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Endosomal Sorting Complexes Required for Transport / genetics*
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Endosomal Sorting Complexes Required for Transport / metabolism
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Gene Expression Regulation, Neoplastic*
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Gene Knockdown Techniques
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Humans
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Multiple Myeloma / drug therapy
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Multiple Myeloma / genetics*
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Multiple Myeloma / metabolism
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Phenotype
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Phosphorylation
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Proto-Oncogene Proteins c-akt
Substances
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Endosomal Sorting Complexes Required for Transport
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Adenosine Triphosphatases
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ATPases Associated with Diverse Cellular Activities
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VPS4B protein, human