Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin
Caveolin-1 is suggesyed to act as a tumor suppressor. We tested the hypothesis that caveolin-1 does so by repression of survivin, an Inhibitor of apoptosis protein that regulates cell-cycle progression as well as apoptosis and is commonly overexpressed in human cancers. Ectopic expression of caveolin-1 in HEK293T and ZR75 cells or siRNA-mediated silencing of caveolin-1 in NIH3T3 cells caused downregulation or upregulation of survivin mRNA and protein, respectively. Survivin downregulation in HEK293T cells was paralleled by reduced cell proliferation, increases in G0-G1 and decreases in G2-M phase of the cell cycle. In addition, apoptosis was evident, as judged by several criteria. Importantly, expression of green fluorescent protein-survivin in caveolin-1-transfected HEK293T cells restored cell proliferation and viability. In addition, expression of caveolin-1 inhibited transcriptional activity of a survivin promoter construct in a Î²-catenin-Tcf/Lef-dependent manner. Furthermore, in HEK293T cells caveolin-1 associated with Î²-catenin and inhibited Tcf/Lef-dependent transcription. Similar results were obtained upon caveolin-1 expression in DLD1 cells, where APC mutation leads to constitutive activation of Î²-catenin-Tcf/Lef-mediated transcription of survivin. Taken together, these results suggest that anti-proliferative and proapoptotic properties of caveolin-1 may be attributed to reduced survivin expression via a mechanism involving diminished Î²-catenin-Tcf/ Lef-dependent transcription.
|Título según WOS:||Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin|
|Título según SCOPUS:||Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin|
|Título de la Revista:||JOURNAL OF CELL SCIENCE|
|Editorial:||COMPANY BIOLOGISTS LTD|
|Fecha de publicación:||2006|
|Página de inicio:||1812|