Lay summary
Although ~90% of cancer deaths are caused by metastasis, the underlying molecular events that drive it are poorly understood. This limited understanding hinders the development of effective cancer treatments. Initially thought to be driven by genetic mutations, our work indicates that epigenetic changes such as DNA methylation may be responsible for driving metastasis. Until recently it has not been possible to directly demonstrate that specific methylation changes alter metastatic potential. However, the development of precision editing tools now provides an opportunity to specifically edit epigenetic states target genes and to exclusively investigate the effect of these changes on cancer cell function. Our proposed research will further develop CRISPR/Cas technology to enable high-throughput interrogation of epigenetic drivers of metastasis. We aim to demonstrate that epigenetic mechanisms drive metastasis. This will open new avenues for understanding metastasis biology, lead to better outcome prediction, and identify new therapeutic targets to treat metastatic cancers.