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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
- Source :
- MOLECULAR AND CELLULAR BIOLOGY, Artículos CONICYT, CONICYT Chile, instacron:CONICYT
- Publication Year :
- 2007
- Publisher :
- AMERICAN SOCIETY FOR MICROBIOLOGY, 2007.
-
Abstract
- 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 beta-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 beta-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 beta-catenin-Tcf/Lef-dependent transcription and survivin expression, as seen in HT29(ATCC) cells. In addition, coimmunoprecipitation and colocalization between caveolin-1 and beta-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 beta-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.
- Subjects :
- Transcription, Genetic
Lymphoid Enhancer-Binding Factor 1
Survivin
Caveolin 1
Down-Regulation
Apoptosis
Biology
Inhibitor of apoptosis
Inhibitor of Apoptosis Proteins
Mice
Dogs
Genes, Reporter
Cell Line, Tumor
Animals
Humans
Immunoprecipitation
Molecular Biology
neoplasms
beta Catenin
Regulation of gene expression
Cell Nucleus
HEK 293 cells
Cell Biology
Articles
Cadherins
digestive system diseases
Cell biology
Clone Cells
Neoplasm Proteins
Gene Expression Regulation, Neoplastic
Cell culture
Tumor progression
Catenin
Cancer research
TCF Transcription Factors
Microtubule-Associated Proteins
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- MOLECULAR AND CELLULAR BIOLOGY, Artículos CONICYT, CONICYT Chile, instacron:CONICYT
- Accession number :
- edsair.doi.dedup.....87e6d2be8e1439daf59edd01d63b2883