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BMI1, a polycomb group PcG protein, plays a critical role in epigenetic regulation of cell differentiation and proliferation, and cancer stem cell self-renewal. BMI1 is upregulated in multiple types of cancer, including prostate cancer. More importantly, we demonstrate that targeting BMI1 effectively inhibits tumor growth of xenografts that have developed resistance to surgical castration and enzalutamide treatment.
These results suggest that blocking BMI1 alone or in combination with anti-AR therapy can be more efficient to suppress prostate tumor growth.
Polycomb group PcG proteins are essential for determining cell differentiation, maintaining stem cell self-renewal, and regulating cellular memories and proliferation 1 , 2.
PcG proteins are known to exert their functions by forming multimeric chromatin-associated protein complexes and repressing downstream targets. The two polycomb repressive complexes PRC1 and PRC2 are major epigenetic regulators for monoubiquitination of histone H2A at lysine and methylation of histone H3 at lysine BMI1 is abundantly expressed in prostatic luminal epithelial cells and its levels are associated with poor prognosis of prostate cancer patients 5. These findings suggest that BMI1 may have functions other than stem cell renewal capacity that has not been fully characterized.
