Project description:Through analysis of a high-content screen we discovered that mir-203 can impair cell migration by suppressing p63 expression. We further determined that p63 promotes motility by inducing the expression of multiple target genes. Total RNA isolated from cell lines with different rated of motility was compared.
Project description:Through analysis of a high-content screen we discovered that mir-203 can impair cell migration by suppressing p63 expression. We further determined that p63 promotes motility by inducing the expression of multiple target genes. Total RNA isolated from cell lines with different rated of motility was compared.
Project description:Through analysis of a high-content screen we discovered that mir-203 can impair cell migration by suppressing p63 expression. We further determined that p63 promotes motility by inducing the expression of multiple target genes.
Project description:Through analysis of a high-content screen we discovered that mir-203 can impair cell migration by suppressing p63 expression. We further determined that p63 promotes motility by inducing the expression of multiple target genes.
Project description:Cell migration is a critical step in cancer cell invasion. Recent studies have implicated the importance of the extracellular signal-regulated kinase (ERK) signaling pathway in cancer cell migration. However, the mechanism associated with ERK-regulated cell migration is poorly understood. Using a panel of breast cancer cell lines, we detected an excellent correlation between ERK activity and cell migration. Interestingly, we noticed that a 48-hour treatment with U0126 [specific mitogen-activated protein/ERK kinase (MEK)-1/2 inhibitor] was needed to significantly inhibit breast cancer cell migration, whereas this inhibitor blocked ERK activity within 1 hour. This observation suggests that ERK-dependent gene expression, rather than direct ERK signaling, is essential for cell migration. With further study, we found that ERK activity promoted the expression of the activator protein-1 (AP1) components Fra-1 and c-Jun, both of which were necessary for cell migration. Combination of U0126 treatment and Fra-1/c-Jun knockdown did not yield further reduction in cell migration than either alone, indicating that ERKs and Fra-1/c-Jun act by the same mechanism to facilitate cell migration. In an attempt to investigate the role of Fra-1/c-Jun in cell migration, we found that the ERK-Fra-1/c-Jun axis regulated slug expression in an AP1-dependent manner. Moreover, the occurrence of U0126-induced migratory inhibition coincided with slug reduction, and silencing slug expression abrogated breast cancer cell migration. These results suggest an association between ERK-regulated cell migration and slug expression. Indeed, cell migration was not significantly inhibited by U0126 treatment or Fra-1/c-Jun silencing in cells expressing slug transgene. Our study suggests that the ERK pathway regulates breast cancer cell migration by maintaining slug expression.