MCAM/MUC18 REGULATES MELANOMA PROGRESSION BY MODULATING THE EXPRESSION OF ID-1

The acquisition of the metastatic melanoma phenotype is associated with increased expression of the melanoma cell adhesion molecule MCAM/MUC18 (CD146). However, the mechanism by which MUC18 contributes to melanoma metastasis remains unclear. Herein, we stably silenced MUC18 expression utilizing lentivirus-incorporated small hairpin RNA, in two metastatic melanoma cell lines, A375SM and C8161, and conducted cDNA microarray analysis. We identified and validated that the transcriptional regulator, Inhibitor of DNA Binding-1 (Id-1), previously shown to function as an oncogene in several malignancies, was downregulated by 5.6-fold following MUC18 silencing. Additionally, we found that MUC18 regulated Id-1 expression at the transcriptional level via ATF-3. Interestingly, ATF-3 was upregulated by 6.9 fold in our cDNA microarray analysis following MUC18 silencing. ChIP analysis showed increased binding of ATF-3 to the Id-1 promoter after MUC18 silencing, while mutation of the ATF-3 binding site on the Id-1 promoter increased Id-1 promoter activity in MUC18-silenced cells. These Data suggest that MUC18 silencing promotes inhibition of Id-1 expression by increasing ATF-3 expression and binding to the Id-1 promoter. Rescue of MUC18 reverted the expression of Id-1 and ATF-3, thus validating that they are not off-target effects of MUC18. To further assess the role of Id-1 in melanoma invasion and metastasis, we overexpressed Id-1 in MUC18-silenced cells. Overexpression of Id-1 in MUC18-silenced cells resulted in increased cell invasion, as well as increased expression and activity of MMP-2. Our data further reveal that Id-1 regulates MMP-2 at the transcriptional level through Sp1 and Ets-1. This is the first report to demonstrate that MUC18 does not act exclusively in cell adherence, but is also involved in cell signaling that regulates the expression of genes, such as Id-1 and ATF-3, thus contributing to the metastatic melanoma phenotype.

Chipping Away at the Monolith: Dispelling the Myth of Father Noninvolvement in Children's Early Literacy Development

Current research stresses the importance of parent involvement in their children 's academic development. Parents reading and writing with their young children is shown to prepare them for the benefits of for ma I education. Studies completed on parent participation in early literacy activities have tended to look at mothers ' role. Few researchers have investigated the contributions fathers have made. The results of a study completed on father-child early literacy practices are presented. Fathers reported engaging in reading and writing activities with their children for three reasons: To prepare their children for school, to bond with their children, and to assist their children in language skill development. Recommendations are provided on how to encourage fathers to participate in early literacy practices

Beyond Bullying: Transforming the Culture of Peer Abuse

Bullying needs to be understood and positioned as a form of child abuse – peer abuse. For too many people, bullying is a benign term. This article will include information collected from a wide-range of researchers and discussions with over 50,000 students that I have facilitated during the past twenty years. The content will focus on new morbidities related to bullying such as depression and suicide, obesity, eating disorders, food allergies, juvenile diabetes, truancy, and substance and alcohol abuse. Making a cultural change in our society will require identified Change Agents, along with recommendations for collaboration, policies, projects and legislation.