RNA-Seq of brain metastatic breast cancer cell lines after knockout of lipid metabolism genes using CRISPR/Cas9 gene editing

Brain metastasis is one of the lethal causes of breast cancer. Here we identified an altered lipid metabolism state to be associated with brain metastatic potential of breast cancer cell lines. To investigate the mechanism, we knocked out genes mediating this altered state and examined transcriptomic changes. The results revealed that these genes confer cells a state with increased lipid and cholesterol biosynthesis and that resembles the lipid metabolite state seen in the brain. These findings revealed an unappreciated machinery that cancer cells adopt for their increased adaptability to the brain microenvironment. Overall design: CRISPR/Cas9-expressing versions of the cell lines were infected with guides targeting sterol regulatory element-binding protein 1 (SREBF1), SREBP cleavage-activating protein (SCAP), phosphomevalonate kinase (PMVK) or non-targeting controls. Knock-out and wild-type cells were profiled with RNA-Seq. Profiling was performed for four brain metastatic breast cell lines including MDAMB231, HCC1806, HCC1954, and JIMT1.