期刊
TRANSLATIONAL ONCOLOGY
卷 19, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2022.101386
关键词
Breast cancer; Tamoxifen; Acetyl-CoA synthetases; ACSS1; ACSS2; Estrogen receptor-alpha
类别
资金
- National Cancer Institute [R01CA200232-05]
- DoD breast cancer grant [W81XWH-16-1-0025]
Acetyl-CoA synthetases ACSS1 and ACSS2 are important for breast cancer cell survival in 4-OHT-treated and long-term estrogen deprived cells.
Acetyl-CoA synthetases ACSS1 and ACSS2 promote conversion of acetate to acetyl-CoA for use in lipid synthesis, protein acetylation, and energy production. These enzymes are elevated in some cancers and important for cell survival under hypoxia and nutrient stress. 4-hydroxytamoxifen (4-OHT) can induce metabolic changes that increase cancer cell survival. An effect of 4-OHT on expression of ACSS1 or ACSS2 has not been reported. We found ACSS1 and ACSS2 are increased by 4-OHT in estrogen receptor-alpha positive (ER+) breast cancer cells and 4-OHT resistant derivative cells. ER alpha knockdown blocked ACSS1 induction by 4-OHT but not ACSS2. 4-OHT also induced ACSS2 but not ACSS1 expression in triple negative breast cancer cells. Long-term estrogen deprivation (LTED) is a model for acquired resistance to aromatase inhibitors. We found LTED cells and tumors express elevated levels of ACSS1 and/or ACSS2 and are especially sensitive to viability loss caused by depletion of ACSS1 and ACSS2 or treatment with an ACSS2-specific inhibitor. ACSS2 inhibitor also increased toxicity in cells treated with 4-OHT. We conclude ACSS1 and ACSS2 are 4-OHT regulated factors important for breast cancer cell survival in 4-OHT-treated and long-term estrogen deprived cells.
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