Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib

Klaus Podar, Reshma Shringarpure, Yu-Tzu Tai, Melissa Simoncini, Martin Sattler, Kenji Ishitsuka, Paul G Richardson, Teru Hideshima, Dharminder Chauhan, Kenneth C Anderson

Research output: Journal article (peer-reviewed)Journal article

90 Citations (Scopus)


We recently demonstrated that caveolae, vesicular flask-shaped invaginations of the plasma membrane, represent novel therapeutic targets in multiple myeloma. In the present study, we demonstrate that vascular endothelial growth factor (VEGF) triggers Src-dependent phosphorylation of caveolin-1, which is required for p130(Cas) phosphorylation and multiple myeloma cell migration. Conversely, depletion of caveolin-1 by antisense methodology abrogates p130(Cas) phosphorylation and VEGF-triggered multiple myeloma cell migration. The proteasome inhibitor bortezomib both inhibited VEGF-triggered caveolin-1 phosphorylation and markedly decreased caveolin-1 expression. Consequently, bortezomib inhibited VEGF-induced multiple myeloma cell migration. Bortezomib also decreased VEGF secretion in the bone marrow microenvironment and inhibited VEGF-triggered tyrosine phosphorylation of caveolin-1, migration, and survival in human umbilical vascular endothelial cells. Taken together, these studies demonstrate the requirement of caveolae for VEGF-triggered multiple myeloma cell migration and identify caveolin-1 in multiple myeloma cells and human umbilical vascular endothelial cells as a molecular target of bortezomib.

Original languageEnglish
Pages (from-to)7500-7506
Number of pages7
JournalCancer Research
Issue number20
Publication statusPublished - 15 Oct 2004
Externally publishedYes


  • Antineoplastic Agents/pharmacology
  • Bone Marrow/metabolism
  • Boronic Acids/pharmacology
  • Bortezomib
  • Caveolin 1
  • Caveolins/biosynthesis
  • Cell Line, Tumor
  • Cell Movement/drug effects
  • Crk-Associated Substrate Protein
  • Endothelium, Vascular/cytology
  • Humans
  • Multiple Myeloma/genetics
  • Phosphorylation
  • Proteins/metabolism
  • Pyrazines/pharmacology
  • Recombinant Proteins/pharmacology
  • Retinoblastoma-Like Protein p130
  • Transfection
  • Tyrosine/metabolism
  • Vascular Endothelial Growth Factor A/antagonists & inhibitors
  • src-Family Kinases/metabolism


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