Document Detail


Widespread deregulation of phosphorylation-based signaling pathways in multiple myeloma cells: opportunities for therapeutic intervention.
MedLine Citation:
PMID:  21541441     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multiple myeloma (MM) is a neoplasm of plasma cell origin that is largely confined to the bone marrow (BM). Chromosomal translocations and other genetic events are known to contribute to deregulation of signaling pathways that lead to transformation of plasma cells and progression to malignancy. However, the tumor stroma may also provide trophic support and enhance resistance to therapy. Phosphorylation of proteins on tyrosine, serine and threonine residues plays a pivotal role in cell growth and survival. Therefore, knowing the status of phosphorylation-based signaling pathways in cells may provide key insights into how cell growth and survival is promoted in tumor cells. To provide a more comprehensive molecular analysis of signaling disruptions in MM, we conducted a kinome profile comparison of normal plasma cells and MM plasma cells as well as their surrounding cells from normal BM and diseased BM. Integrated pathway analysis of the profiles obtained reveals deregulation of multiple signaling pathways in MM cells but also in surrounding bone marrow blood cells compared to their normal counterparts. The deregulated kinase activities identified herein, which include the mTOR (mammalian target of rapamycin)/p70S6K and ERK1/2 (extracellular signal-regulated kinases 1 and 2) pathways, are potential novel molecular targets in this lethal disease.
Authors:
Gwenny Manel Fuhler; Sander Henricus Diks; Maikel Petrus Peppelenbosch; William Garrow Kerr
Publication Detail:
Type:  Journal Article     Date:  2011-04-28
Journal Detail:
Title:  Molecular medicine (Cambridge, Mass.)     Volume:  17     ISSN:  1528-3658     ISO Abbreviation:  Mol. Med.     Publication Date:  2011  
Date Detail:
Created Date:  2011-08-02     Completed Date:  2011-12-27     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  9501023     Medline TA:  Mol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  790-8     Citation Subset:  IM    
Affiliation:
Department of Gasteroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Bone Marrow Cells / metabolism
Cell Line, Tumor
Cell Proliferation
Cell Survival
Cells, Cultured
Humans
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Multiple Myeloma / metabolism*,  pathology,  physiopathology*
Phosphoproteins / metabolism
Phosphorylation
Phosphotransferases / metabolism*
Plasma Cells / metabolism
Proteomics / methods
Ribosomal Protein S6 Kinases, 70-kDa / metabolism
Signal Transduction*
TOR Serine-Threonine Kinases / metabolism
Chemical
Reg. No./Substance:
0/Phosphoproteins; EC 2.7.-/Phosphotransferases; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa; EC 2.7.11.24/MAPK1 protein, human; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3
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