E-cadherin is required for caveolin-1-mediated down-regulation of the inhibitor of apoptosis protein survivin via reduced beta-Catenin-Tcf/Lef-dependent transcription
Caveolin-1 reportedly acts as a tumor suppressor and promotes events associated with tumor progression, including metastasis. The molecular mechanisms underlying such radical differences in function are not understood. Recently, we showed that caveolin-1 inhibits expression of the inhibitor of apoptosis protein survivin via a transcriptional mechanism involving the Î²-catenin-Tcf/Lef pathway. Surprisingly, while caveolin-1 expression decreased survivin mRNA and protein levels in HT29(ATCC) human colon cancer cells, this was not the case in metastatic HT29(US) cells. Survivin down-regulation was paralleled by coimmunoprecipitation and colocalization of caveolin-1 with Î²-catenin in HT29(ATCC) but not HT29(US) cells. Unlike HT29(ATCC) cells, HT29(US) cells expressed small amounts of E-cadherin that accumulated in intracellular patches rather than at the cell surface. Re-expression of E-cadherin in HT29(US) cells restored the ability of caveolin-1 to down-regulate Î²-catenin-Tcf/Lef-dependent transcription and survivin expression, as seen in HT29(ATCC) cells. In addition, coimmunoprecipitation and colocalization between caveolin-1 and Î²-catenin increased upon E-cadherin expression in HT29(US) cells. In human embryonic kidney HEK293T and HT29(US) cells, caveolin-1 and E-cadherin cooperated in suppressing Î²-catenin-Tcf/ Lef-dependent transcription as well as survivin expression. Finally, mouse melanoma B16-F10 cells, another metastatic cell model with low endogenous caveolin-1 and E-cadherin levels, were characterized. In these cells, caveolin-1-mediated down-regulation of survivin in the presence of E-cadherin coincided with increased apoptosis. Thus, the absence of E-cadherin severely compromises the ability of caveolin-1 to develop activities potentially relevant to its role as a tumor suppressor. Copyright Â© 2007, American Society for Microbiology. All Rights Reserved.
|Título según WOS:||E-cadherin is required for caveolin-1-mediated down-regulation of the inhibitor of apoptosis protein survivin via reduced beta-Catenin-Tcf/Lef-dependent transcription|
|Título según SCOPUS:||E-cadherin is required for caveolin-1-mediated down-regulation of the inhibitor of apoptosis protein survivin via reduced ß-catenin-Tcf/Lef- dependent transcription|
|Título de la Revista:||MOLECULAR AND CELLULAR BIOLOGY|
|Editorial:||AMER SOC MICROBIOLOGY|
|Fecha de publicación:||2007|
|Página de inicio:||7703|