The Role of Prmt1 in Osteosarcoma Initiation and Metastasis
Osteosarcoma (OS) is the most common bone cancer, afflicting mostly children and young adults. Despite efforts in the past 30 years, treatment against this devastating disease has not improved significantly. Thus, there is an urgent need to develop novel therapeutic strategy to help improve the overall survival rate of OS patients. Our lab has recently generated genetically engineered mice that closely model human OS. Using OS cell lines derived from our engineered mice and genome-wide RNAi screening technology, we have found many genes, upon inactivation, selectively kill OS cells. Interestingly, one of our highest ranked candidate genes, Prmt1, belongs to a group of proteins, termed "epigenetic modifiers." Epigenetic modifiers can modify DNA to turn on or off gene expression.
Emerging evidence has suggested that abnormal activity of epigenetic modifiers can lead to cancerous growth. Our preliminary study suggests that depletion of Prmt1 expression impairs tumor growth in tissue culture dishes and in mice.
Building on our preliminary data, this proposal will determine whether Prmt1 is required for the development and metastasis of OS in engineered OS mice. We will identify molecular pathways associated with Prmt1 to expose many more cancer-specific vulnerabilities and potential druggable targets. Our overall goal is to evaluate whether targeting Prmt1 and its associated pathways will be successful at eradicating the disease in a preclinical setting. Our study will offer valuable insights into pathways essential for OS progression and guide future development of more effective, less toxic, therapeutic strategies against this devastating disease.