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Mol. Cell. Biol. doi:10.1128/MCB.01991-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

E-cadherin Is Required for Caveolin-1-Mediated Down-Regulation of the Inhibitor of Apoptosis Protein Survivin Via Reduced -Catenin-Tcf/Lef-Dependent Transcription

Laboratory of Cellular Communications, FONDAP Center for Molecular Studies of the Cell (CEMC), Facultad de Medicina, Universidad de Chile, Santiago, Chile

^* To whom correspondence should be addressed. Email: aquest{at}med.uchile.cl.

	Abstract

Caveolin-1 reportedly acts both 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 -catenin-Tcf/Lef pathway. Surprisingly, while in HT29(ATCC) human colon cancer cells, caveolin-1 expression decreased survivin mRNA and protein levels, this was not the case in metastatic HT29(US) cells. Survivin down-regulation was paralleled by co-immunoprecipitation and co-localization of caveolin-1 with -catenin in HT29(ATCC), but not HT29(US) cells. Unlike HT29(ATCC) cells, HT29(US) cells expressed low 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 both to down-regulate -catenin-Tcf/Lef-dependent transcription and survivin expression, as seen in HT29(ATCC) cells. In addition, co-immunoprecipitation and co-localization between caveolin-1 and -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 -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, absence of E-cadherin severely compromises the ability of caveolin-1 to develop activities potentially relevant to its role as a tumor suppressor.