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

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 ␤-catenin-Tcf/Lef pathway. Surprisingly, while caveolin-1 expression decreased survivin mRNA and protein levels in HT29 (

Disruption of xCT inhibits cancer cell metastasis via the caveolin-1/β-catenin pathway

“…Several studies have shown that caveolin-1 functions as an important player in Wnt-independent regulation of transcriptional activity of b-catenin (Lu et al, 2003;Lu and Hunter, 2004). Caveolin-1 recruits b-catenin to caveolae membranes for its link with E-cadherin and thus promotes cell adhesion and effectively inhibits b-catenin TCF/LEF-1 signaling (Galbiati et al, 2000;Torres et al, 2007). In addition, caveolin-1 was reported to colocalize with a variety of lipid-modified signaling molecules, including G proteins, Src-like kinases, HaRas and eNOS on caveolae membranes, and function as a negative regulator of these proteins (Li et al, 1996;Couet et al, 1997;Okamoto et al, 1998).…”

“…On the other side, caveolin-1 directs the distribution of E-cadherin and increases E-cadherin expression by downregulation of transcriptional repressor snail (Volonte et al, 1999;Lu et al, 2003), and E-cadherin is required for caveolin-1-mediated reduction of b-catenin-TCF/LEF-dependent transcription (Torres et al, 2007). E-cadherin is also known to negatively regulate b-catenin-mediated cell adhesion and transcription by altering its subcellular distribution.…”

Different responses in transformation of MDCK cells in 2D and 3D culture by v-Src as revealed by microarray techniques, RT-PCR and functional assays

“…Caveolin-1 inhibits expression of survivin, associates with b-catenin and regulates clathrin-independent endocytosis of cadherin. 44 Nanos, a p120catenin-binding protein, disturbs E-cadherin-dependent cell-cell adhesion by inducing relocalization of junctional proteins to the cytoplasm. 25 Hence, there is a close link between the existence of tight cellcell adhesion, proliferation and apoptosis in the processes of epithelial differentiation or transformation and p120catenin together with b-catenin has a central role in the regulatory pathways as components of the cell-cell junctions and as regulators of gene expression.…”

Caveolin-1 promotes pancreatic cancer cell differentiation and restores membranous E-cadherin via suppression of the epithelial-mesenchymal transition

“…After fixation, cells were washed three inhibits the β-catenin-TCF oncogenic pathway. 46 Loss of E-cadherin in high grade tumors may promote Cav-1 interaction with other partners, such as FASN, and induce an oncogenic switch in Cav-1 function. However, the relation of Cav-1 and E-cadherin appears to be important to determine the behavior of Cav-1, which in turn deeply affects the behavior of pancreatic cancer cells.…”