2023 STAR Scholar
Title: Identification of novel ACSS2 inhibitors in regulating breast cancer brain metastatic growth
Triple negative breast cancer is an aggressive cancer with an overall survival rate of months when it spreads to the brain. There is no effective drug treatment for brain metastasis patients, thus novel therapies are urgently needed. Breast cancer cells that metastasize to the brain are dependent on fatty acids for growth. The acetyl CoA synthetase 2 (ACSS2) enzyme converts acetate to acetyl CoA, which is critical for the fatty acid production in tumors in the brain. The Reginato lab previously showed that genetically targeting ACSS2 can reduce the growth of breast cancer brain metastasis (BCBM) cells and identified novel ACSS2 inhibitors that show promise using in vivo models of breast cancer brain metastasis. Here, we show that treating BCBM cells with new second generation ACSS2 inhibitors 2749, 7033, and 4855 was able to block BCBM growth in crystal violet assays. Using western blotting, we show that novel ACSS2 inhibitors like 4855 lead to a reduction in E2F1: a downstream protein of the ACSS2. These results identify ACSS2 inhibitor 4855 as a potent inhibitor of BCBM cell growth and supports further testing of these novel ACSS2 inhibitors as novel therapeutic agents for the treatment of breast cancer brain metastatic growth.
Title: Identification of novel ACSS2 inhibitors in regulating breast cancer brain metastatic growth
Triple negative breast cancer is an aggressive cancer with an overall survival rate of months when it spreads to the brain. There is no effective drug treatment for brain metastasis patients, thus novel therapies are urgently needed. Breast cancer cells that metastasize to the brain are dependent on fatty acids for growth. The acetyl CoA synthetase 2 (ACSS2) enzyme converts acetate to acetyl CoA, which is critical for the fatty acid production in tumors in the brain. The Reginato lab previously showed that genetically targeting ACSS2 can reduce the growth of breast cancer brain metastasis (BCBM) cells and identified novel ACSS2 inhibitors that show promise using in vivo models of breast cancer brain metastasis. Here, we show that treating BCBM cells with new second generation ACSS2 inhibitors 2749, 7033, and 4855 was able to block BCBM growth in crystal violet assays. Using western blotting, we show that novel ACSS2 inhibitors like 4855 lead to a reduction in E2F1: a downstream protein of the ACSS2. These results identify ACSS2 inhibitor 4855 as a potent inhibitor of BCBM cell growth and supports further testing of these novel ACSS2 inhibitors as novel therapeutic agents for the treatment of breast cancer brain metastatic growth.