title: Inhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.
abstract: High throughput DNA microarray has made it possible to outline genes whose expression in malignant plasma cells is associated with short overall survival of patients with Multiple Myeloma (MM). A further step is to elucidate the mechanisms encoded by these genes yielding to drug resistance and/or patients' short survival. We focus here on the biological role of the DEP (for Disheveled, EGL-10, Pleckstrin) domain contained protein 1A (DEPDC1A), a poorly known protein encoded by DEPDC1A gene, whose high expression in malignant plasma cells is associated with short survival of patients. Using conditional lentiviral vector delivery of DEPDC1A shRNA, we report that DEPDC1A knockdown delayed the growth of human myeloma cell lines (HMCLs), with a block in G2 phase of the cell cycle, p53 phosphorylation and stabilization, and p21(Cip1) accumulation. DEPDC1A knockdown also resulted in increased expression of mature plasma cell markers, including CXCR4, IL6-R and CD38. Thus DEPDC1A could contribute to the plasmablast features of MMCs found in some patients with adverse prognosis, blocking the differentiation of malignant plasma cells and promoting cell cycle.
authors: INSERM, U1040, Montpellier, France.
authors: Alboukadel
authors: A
authors: Kassambara
authors: Matthieu
authors: M
authors: Schoenhals
authors: Jérôme
authors: J
authors: Moreaux
authors: Jean-Luc
authors: JL
authors: Veyrune
authors: Thierry
authors: T
authors: Rème
authors: Hartmut
authors: H
authors: Goldschmidt
authors: Dirk
authors: D
authors: Hose
authors: Bernard
authors: B
authors: Klein
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016000:Cluster Analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D020690:GTPase-Activating Proteins; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D055550:Protein Stability; D034622:RNA Interference; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; C584411:DEPDC1 protein, human; D020690:GTPase-Activating Proteins; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53
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