Caveolin-1 in oncogenic transformation, cancer, and metastasis

被引:448
作者
Williams, TM
Lisanti, MP
机构
[1] Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA
[2] Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA
[3] Yeshiva Univ Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2005年 / 288卷 / 03期
关键词
caveolae; cellular signaling; tumor formation; cell invasiveness;
D O I
10.1152/ajpcell.00458.2004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Caveolae are 50- to 100-nm omega-shaped invaginations of the plasma membrane that function as regulators of signal transduction. Caveolins are a class of oligomeric structural proteins that are both necessary and sufficient for caveolae formation. Interestingly, caveolin-1 has been implicated in the pathogenesis of oncogenic cell transformation, tumorigenesis, and metastasis. Here, we review the available experimental evidence ( gleaned from cultured cells, animal models, and human tumor samples) that caveolin-1 (Cav-1) functions as a "tumor and/or metastasis modifier gene." Genetic evidence from the study of Cav-1( -/-) null mice and human breast cancer mutations [CAV-1 (P132L)] supports the idea that caveolin-1 normally functions as a negative regulator of cell transformation and mammary tumorigenesis. In contrast, caveolin-1 may function as a tumor promoter in prostate cancers. We discuss possible molecular mechanisms to explain these intriguing, seemingly opposing, findings. More specifically, caveolin-1 phosphorylation ( at Tyr14 and Ser80) and mutations ( P132L) may override or inactivate the growth inhibitory activity of the caveolin-scaffolding domain ( residues 82 - 101).
引用
收藏
页码:C494 / C506
页数:13
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