CtBP promote the cancer cell migration through downregulating cholesterol synthesis

• 作 者: Zhiqiang Zhao Li Wang Lijun Di
• 机 构: Faculty of Health Sciences,University of Macau,Macau SAR,China
• 出 处: 中国生物化学与分子生物学会2016年全国学术会议
• 发表日期: 2016年3期
• 关键词: CtBP Cholesterol EMT Cancer

　　Cancermetastasis kills almost 90%of patient and almost always announces the worst destination of patients once being diagnosed.How the tumor cells eventually turn to metastatic cells is still unclear but the epithelial to mesenchymal transition is believed to be essential in the metastasis process.Along this process,cells experience significant alteration in gene expression profiles,cell organization,energy production and metabolic activities etc.CtBP is a known co-repressor factor involved in regulating gene expression.Recent studies also found that CtBP is important for promoting cancer cell growth,increasing EMT,stabilizing cancerous metabolism etc.Now we found that CtBP is important regulator of cell metabolism pathways.Specifically,we found CtBP inhibits cholesterol synthesis in cancer cells.Since cholesterol is recently known to be critical player in influencing the membrane fluidity and the cell migration ability,as well as the cancer cell metastasis,we wonder if CtBP regulates cancer metastasis through repressing cholesterol content.Both the woundhealing assay and the transwell assay were applied to demonstrated that CtBP promotes the cell migration which can be abolished by cholesterol treatment and enhanced by statin,the inhibitor of cholesterol synthesis.These results indicate that CtBP promoted cancer cell migration is at least partially through regulating the abundance of cholesterol.Actually,by using filipin staining,we were able to show that the membrane bound cholesterol is reduced by CtBP.Together,our data demonstrated a novel pathway through which CtBP represses the cholesterol in cancer cells and increases the fluidity of membrane which is essential for cell migration and metastasis.