부산대 / 손범석, 윤부현*
전사인자 Ets1에 의해서 조절되는 FBP1의 발현이 방사선 치료 이후 생존한 악성 뇌종양 세포에서 높은 발현을 보였으며, 이에 따라 FBP1의 발현이 더욱 감소하게 되어 glycolysis가 활성화되게 된다. 이를 억제하기 위하여 glycolysis 과정에 관여하는 PGAM의 선택적 저해제를 통해서 GBM의 악성화를 억제하고 치료 저항성을 낮추어 치료 효율을 높일 수 있다.
Radiotherapy is a standard treatment option for patients with glioblastoma (GBM). Although it has high therapeutic efficacy, some proportion of the tumor cells that survive after radiotherapy may cause side effects. In this study, we found that fructose 1,6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis, was downregulated upon treatment with ionizing radiation (IR). Ets1, which was found to be overexpressed in IR-induced infiltrating GBM, was suggested to be a transcriptional repressor of FBP1. Furthermore, glucose uptake and extracellular acidification rates were increased upon FBP1 downregulation, which indicated an elevated glycolysis level. We found that emodin, an inhibitor of phosphoglycerate mutase 1 derived from natural substances, significantly suppressed the glycolysis rate and IR-induced GBM migration in in vivo orthotopic xenograft mouse models. We propose that the reduced FBP1 level reprogrammed the metabolic state of GBM cells, and thus, FBP1 is a potential therapeutic target regulating GBM metabolism following radiotherapy.
Son B1, Lee S1, Kim H1, Kang H1, Jeon J1,2, Jo S2, Seong KM3, Lee SJ4, Youn H5, Youn B6,7.
Department of Integrated Biological Science, Pusan National University, Busan, 46241, Republic of Korea.
Department of Radiation Oncology, Haeundae Paik Hospital, Inje University School of Medicine, Busan, 48108, Republic of Korea.
Laboratory of Low Dose Risk Assessment, National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Republic of Korea.
Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea.
Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, 05006, Republic of Korea.
Department of Integrated Biological Science, Pusan National University, Busan, 46241, Republic of Korea. email@example.com.
Department of Biological Sciences, Pusan National University, Busan, 46241, Republic of Korea. firstname.lastname@example.org.