Beta-Catenin Downregulation Contributes to Epidermal Growth Factor-induced Migration and Invasion of MDAMB231 Cells
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We previously demonstrated that epidermal growth factor (EGF) enhances cell migration and invasion of breast cancer cells in a SMAD ubiquitination regulatory factor 1 (SMURF1)-dependent manner and that SMURF1 induces degradation of β-catenin in C2C12 cells. However, the relationship between EGF-induced SMURF1 and β-catenin expression in breast cancer cells remains unclear. So, we investigated if EGF and SMURF1 regulate β-catenin expression in MDAMB231 human breast cancer cells. When MDAMB231 cells were incubated with EGF for 24, 48, and 72 hours, EGF significantly increased expression levels of SMURF1 mRNA and protein while suppressing expression levels of β-catenin mRNA and protein. Overexpression of SMURF1 downregulated β-catenin mRNA and protein, whereas knockdown of SMURF1 increased β-catenin expression and blocked EGF-induced β-catenin downregulation. Knockdown of β-catenin enhanced cell migration and invasion of MDAMB231 cells, while β-catenin overexpression suppressed EGF-induced cell migration and invasion. Furthermore, knockdown of β-catenin enhanced vimentin expression and decreased cytokeratin expression, whereas β -catenin overexpression decreased vimentin expression and increased cytokeratin expression. These results suggest that EGF downregulates β-catenin in a SMURF1-dependent manner and that β-catenin downregulation contributes to EGF-induced cell migration and invasion in MDAMB breast cancer cells.
Abstract
We previously demonstrated that epidermal growth factor (EGF) enhances cell migration and invasion of breast cancer cells in a SMAD ubiquitination regulatory factor 1 (SMURF1)-dependent manner and that SMURF1 induces degradation of β-catenin in C2C12 cells. However, the relationship between EGF-induced SMURF1 and β-catenin expression in breast cancer cells remains unclear. So, we investigated if EGF and SMURF1 regulate β-catenin expression in MDAMB231 human breast cancer cells. When MDAMB231 cells were incubated with EGF for 24, 48, and 72 hours, EGF significantly increased expression levels of SMURF1 mRNA and protein while suppressing expression levels of β-catenin mRNA and protein. Overexpression of SMURF1 downregulated β-catenin mRNA and protein, whereas knockdown of SMURF1 increased β-catenin expression and blocked EGF-induced β-catenin downregulation. Knockdown of β-catenin enhanced cell migration and invasion of MDAMB231 cells, while β-catenin overexpression suppressed EGF-induced cell migration and invasion. Furthermore, knockdown of β-catenin enhanced vimentin expression and decreased cytokeratin expression, whereas β -catenin overexpression decreased vimentin expression and increased cytokeratin expression. These results suggest that EGF downregulates β-catenin in a SMURF1-dependent manner and that β-catenin downregulation contributes to EGF-induced cell migration and invasion in MDAMB breast cancer cells.
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