Abstract LB-A12: New target for cancer metabolism : Steroid Sulfatase

Abstract

Abstract Steroid sulfatase (STS) expression has been considered to play a pivotal role in estrogen-dependent cancers. STS is known as a target enzyme for suppressing estrogen-mediated carcinogenesis. STS is able to convert estrogen sulfate to estrone form, like dehydroepiandrosterone sulfate (DHEA-S) to its' active form dehydroepiandrosterone (DHEA). Aerobic glycolysis is a hallmark of cancer metabolism. Lactic acid production was also increased by STS and DHEA.STS and its' major product DEHA reduced Oxygen consumption rate. STX064, a STS specific inhibitor inhibited DHEA formation and lactic acid production, recovered mitochondria resperation in HeLa cells. Hypoxia inducing factor 1 subunit HIF1α is recognized as an important regulator of aerobic glycolysis. To elucidate whether STS is able to regulate cancer metabolism, the effects on aerobic glycolysis were determined. STS overexpression significantly converted DHEA-S to DHEA. STS and the major product DHEA enhanced HIF1α protein, mRNA, promoter activity in HeLa cells. Glycolytic enzymes such as hexokinase 2 (HK-2) and glucose transporter (GLUT) were increased by STS overexpression and DHEA treatment in protein and mRNA levels. When cells were treated with HIF1α siRNA, all glycolytic enzymes induced by STS and DHEA were down-regulated. STS also regulated pyruvate kinase M (PKM)splicing. STS up-regulated PKM2 level and inhibited PKM1 level through transcription factor c-Myc. Phosphorylation of PKM2 was also induced by STS. In conclusion, STS and the major product DHEA may regulate aerobic glycolysis via HIF1α induction and c-Myc related PKM2 alternative splicing. Citation Format: sangyun shin, Yeo-Jung Kwon, Dong-Jin Ye, Hyoung-Seok Baek, Young-Jin Chun. New target for cancer metabolism : Steroid Sulfatase. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-A12.