Abstract 5420: PGAM1-REDD1 pathway promotes paclitaxel resistance through enhancing aerobic glycolysis in ovarian cancer cells

Abstract

Abstract Aerobic glycolysis is a dominant pathway for energy production in cancer cells, but the association of this phenomenon with chemoresistance remains still uncertain. Here, we found that the expression of phosphoglycerate mutase 1 (PGAM1), a key catalytic enzyme in aerobic glycolysis, was significantly higher in paclitaxel-resistant ovarian cancer cell line SKOV3. Up-regulated PGAM1 expression by gene transfection and down-regulated PGAM1 expression by siRNA knockdown altered the process of aerobic glycolysis, paclitaxel sensitivity and DNA damage response 1 (REDD1) expression in ovarian cancer cells (SKOV3 and A2780). Further, the change of the concentration of pyruvic acid or lactic acid in culture medium and REDD1 expression by gene transfection or siRNA knockdown also altered the sensitivity to paclitaxel. REDD1 knockdown of by siRNA reversed partially paclitaxel resistance induced by PGAM1 over-expression in cancer cells, vice versa. Structural interaction between PGAM1 and REDD1 was predicted by molecular docking. Our results suggested that PGAM1-REDD1 pathway promotes paclitaxel resistance through enhancing aerobic glycolysis in ovarian cancer cells. Citation Format: Yan Feng, Weiguo Lv, Xing Xie, Yan Yu. PGAM1-REDD1 pathway promotes paclitaxel resistance through enhancing aerobic glycolysis in ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5420. doi:10.1158/1538-7445.AM2017-5420