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

被引：77

作者：

Podar, K ^{[1
]}

Shringarpure, R ^{[1
]}

Tai, YT ^{[1
]}

Simoncini, M ^{[1
]}

Sattler, M ^{[1
]}

Ishitsuka, K ^{[1
]}

Richardson, PG ^{[1
]}

Hideshima, T ^{[1
]}

Chauhan, D ^{[1
]}

Anderson, KC ^{[1
]}

机构：

[1] Harvard Univ, Dana Farber Canc Inst,Med Sch, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA

来源：

CANCER RESEARCH | 2004年 / 64卷 / 20期

关键词：

D O I：

10.1158/0008-5472.CAN-04-0124

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 Sre-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.

引用

页码：7500 / 7506

页数：7

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[1] Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells [J].