Therapeutic targeting of SET1B/COMPASS pathway in treating triplenegative breast cancer

Mutations within the epigenetic factors are associated with a large number of human cancers. We identified the COMPASS family of histone lysine methyltransferases as the first class of histone methylases involved in epigenetic regulation of gene expression. Our initial studies have demonstrated that SET1B/COMPASS is cytoplasmic and is overexpressed in human breast cancer and that COMPASS overexpression significantly correlates with ER-negative patient survival. Furthermore, our studies showed that the loss of SET1B selectively inhibits multiple triple negative breast cancer cell survivals. Through our genome-wide target screens, we identified AdiopR1 as a target of SET1B/COMPASS and that the agonist of AdiopR1 can stop the growth of triple negative breast cancer similar to that of SET1B/COMPASS loss. We are in the process of analyzing our biochemical isolations of SET1B/COMPASS from triple negative breast cancer cells and identified some possible specific subunits in these cells. Our goals for this project are to identify direct targets of SET1B/CLOMPASS and show that they can be used in the regulation of growth for the triple negative breast cancer cells. Once identified, we will use the mouse model system of triple negative breast cancer and determine which one of the identified pathways/targets function as therapeutic targets of triple negative breast cancer with the hope moving the targets into clinic.