Neuronal Restrictive Silencing Factor Suppresses Key Players in Breast Cancer Metastasis

Abstract

Neuronal Restrictive Silencing Factor (NRSF) is expressed in non‐neuronal tissues throughout the body where it curbs the inappropriate expression of neuronal genes. Recent reports have implicated NRSF as an initiating factor in many brain breast and colon cancers by stimulating cell growth and survival pathways; however which NRSF target genes are responsible for oncogenesis is still unknown. Using databases of known and potential NRSF binding sites in the genome, in coordination with chromatin immunoprecipitation assays, we have identified several positive regulators of the phosphatidylinositol 3 kinase (PI3K) pathway as potential NRSF regulated genes. Knockdown of NRSF in breast epithelial cell lines results in their increased mRNA and proteins levels, as well as PI3K pathway sensitivity. Importantly, we found that many, but not all, cellular functions downstream of the PI3K pathway have also been altered, including cellular metabolism and other survival signaling pathways. Our work aims to assess the importance of these genes and their metabolic consequences in the oncogenic transformation caused by loss of NRSF in epithelial cells.