This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Podar, K. Articles by Anderson, K. C. Search for Related Content PubMed PubMed Citation Articles by Podar, K. Articles by Anderson, K. C.

Caveolin-1 Is Required for Vascular Endothelial Growth Factor-Triggered Multiple Myeloma Cell Migration and Is Targeted by Bortezomib

Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts

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.

This article has been cited by other articles:

				S. Pan, C. J. World, C. J. Kovacs, and B. C. Berk Glucose 6-Phosphate Dehydrogenase Is Regulated Through c-Src-Mediated Tyrosine Phosphorylation in Endothelial Cells Arterioscler Thromb Vasc Biol, June 1, 2009; 29(6): 895 - 901. [Abstract] [Full Text] [PDF]

				H. E. Moore, E. L. Davenport, E. M. Smith, S. Muralikrishnan, A. S. Dunlop, B. A. Walker, D. Krige, A. H. Drummond, L. Hooftman, G. J. Morgan, et al. Aminopeptidase inhibition as a targeted treatment strategy in myeloma Mol. Cancer Ther., April 1, 2009; 8(4): 762 - 770. [Abstract] [Full Text] [PDF]

				M. S. Raab, I. Breitkreutz, G. Tonon, J. Zhang, P. J. Hayden, T. Nguyen, J. H. Fruehauf, B. K. Lin, D. Chauhan, T. Hideshima, et al. Targeting PKC: a novel role for beta-catenin in ER stress and apoptotic signaling Blood, February 12, 2009; 113(7): 1513 - 1521. [Abstract] [Full Text] [PDF]

				M. Koldehoff, D. W. Beelen, and A. H. Elmaagacli Small-molecule inhibition of proteasome and silencing by vascular endothelial cell growth factor-specific siRNA induce additive antitumor activity in multiple myeloma J. Leukoc. Biol., August 1, 2008; 84(2): 561 - 576. [Abstract] [Full Text] [PDF]

				C. M. Klinge, N. S. Wickramasinghe, M. M. Ivanova, and S. M. Dougherty Resveratrol stimulates nitric oxide production by increasing estrogen receptor {alpha}-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells FASEB J, July 1, 2008; 22(7): 2185 - 2197. [Abstract] [Full Text] [PDF]

				K. M. Bailey and J. Liu Caveolin-1 Up-regulation during Epithelial to Mesenchymal Transition Is Mediated by Focal Adhesion Kinase J. Biol. Chem., May 16, 2008; 283(20): 13714 - 13724. [Abstract] [Full Text] [PDF]

				A. Grande-Garcia, A. Echarri, J. de Rooij, N. B. Alderson, C. M. Waterman-Storer, J. M. Valdivielso, and M. A. del Pozo Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases J. Cell Biol., May 21, 2007; 177(4): 683 - 694. [Abstract] [Full Text] [PDF]

				K. Podar, M. S. Raab, G. Tonon, M. Sattler, D. Barila, J. Zhang, Y.-T. Tai, H. Yasui, N. Raje, R. A. DePinho, et al. Up-Regulation of c-Jun Inhibits Proliferation and Induces Apoptosis via Caspase-Triggered c-Abl Cleavage in Human Multiple Myeloma Cancer Res., February 15, 2007; 67(4): 1680 - 1688. [Abstract] [Full Text] [PDF]

				K. Podar, M. S. Raab, J. Zhang, D. McMillin, I. Breitkreutz, Y.-T. Tai, B. K. Lin, N. Munshi, T. Hideshima, D. Chauhan, et al. Targeting PKC in multiple myeloma: in vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl) Blood, February 15, 2007; 109(4): 1669 - 1677. [Abstract] [Full Text] [PDF]

				T. Hideshima, D. Chauhan, P. Richardson, and K. C. Anderson Identification and Validation of Novel Therapeutic Targets for Multiple Myeloma J. Clin. Oncol., September 10, 2005; 23(26): 6345 - 6350. [Abstract] [Full Text] [PDF]

				S. Dubey and J. H. Schiller Three Emerging New Drugs for NSCLC: Pemetrexed, Bortezomib, and Cetuximab Oncologist, April 1, 2005; 10(4): 282 - 291. [Abstract] [Full Text] [PDF]