AUTHOR=Pallegar Nikitha K., Ayre D. Craig , Christian Sherri L. TITLE=Repression of CD24 surface protein expression by oncogenic Ras is relieved by inhibition of Raf but not MEK or PI3K JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=3 YEAR=2015 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2015.00047 DOI=10.3389/fcell.2015.00047 ISSN=2296-634X ABSTRACT=
CD24 is a dynamically regulated cell surface protein. High expression of CD24 leads to progression of lung, prostrate, colon, and pancreatic cancers, among others. In contrast, low expression of CD24 leads to cell proliferation and metastasis of breast cancer stem cells (BCSCs). Activating mutations in Ras are found in 30% of all human cancers. Oncogenic Ras constitutively stimulates the Raf, PI3K, and Ral GDS signaling pathways, leading to cellular transformation. Previous studies have shown that expression of oncogenic Ras in breast cancer cells generates CD24− cells from CD24+ cells. However, the molecular mechanisms involved in the generation of CD24− cells were not determined. Here, we demonstrate that oncogenic Ras (RasV12) expression suppresses CD24 mRNA, protein, and promoter levels when expressed in NIH/3T3 cells. Furthermore, activation of only the Raf pathway was sufficient to downregulate CD24 mRNA and protein expression to levels similar to those seen in with RasV12 expression. In contrast, activation of the PI3K pathway downregulated mRNA expression with a partial effect on protein expression whereas activation of the RalGDS pathway only partially affected protein expression. Surprisingly, inhibition of MEK with U0126 only partially restored