PMID- 29928884 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 503 IP - 2 DP - 2018 Sep 5 TI - Lactic acid induces lactate transport and glycolysis/OXPHOS interconversion in glioblastoma. PG - 888-894 LID - S0006-291X(18)31404-9 [pii] LID - 10.1016/j.bbrc.2018.06.092 [doi] AB - The Warburg effect is a dominant phenotype of most tumor cells. Recent reports have shown that the Warburg effect can be reprogrammed by the tumor microenvironment. Lactic acidosis and glucose deprivation are the common adverse microenvironments in solid tumor. The metabolic reprogramming induced by lactic acid and glucose deprivation remains to be elucidated in glioblastoma. Here, we show that, under glucose deprivation, lactic acid can preserve high ATP levels and resist cell death in U251 cells. At the same time, we find that MCT1 and MCT4 are significantly highly expressed. The metabolic regulation factor HIF-1alpha decreased and C-MYC increased. Nuclear respiratory factor 1 (NRF1) and oxidative phosphorylation (OXPHOS)-related proteins (NDUFB8, ND1) are all distinctly increased. Therefore, lactic acid can induce lactate transport and convert the dominant Warburg effect to OXPHOS. Through bioinformatics analysis, the high expression of HIF-1alpha, MCT1 or MCT4 indicate a poor prognosis in glioblastoma. In addition, in glioblastoma tissue, HIF-1alpha, MCT4 and LDH are highly expressed in the interior region, and their expression is decreased in the lateral region. MCT1 can not be detected in the interior region and is highly expressed in the lateral region. Hence, different regions of glioblastoma have diverse energy metabolic pathways. Glycolysis occurs mainly in the interior region and OXPHOS in the lateral region. In general, lactic acid can induce regional energy metabolic reprogramming and assist tumor cells to adapt and resist adverse microenvironments. This study provides new ideas for furthering understanding of the metabolic features of glioblastoma. It may promote the development of new therapeutic strategies in GBM. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Duan, Ke AU - Duan K AD - School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China; Key Laboratory for Biochemistry and Molecular Biology of High Education in Yunnan Province, Kunming, Yunnan, 650091, China. FAU - Liu, Zhong-Jian AU - Liu ZJ AD - Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, China. FAU - Hu, Su-Qiong AU - Hu SQ AD - School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China; Key Laboratory for Biochemistry and Molecular Biology of High Education in Yunnan Province, Kunming, Yunnan, 650091, China. FAU - Huo, Hong-Yu AU - Huo HY AD - School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China; Key Laboratory for Biochemistry and Molecular Biology of High Education in Yunnan Province, Kunming, Yunnan, 650091, China. FAU - Xu, Zhi-Ru AU - Xu ZR AD - School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China. FAU - Ruan, Jian-Fei AU - Ruan JF AD - School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China. FAU - Sun, Yang AU - Sun Y AD - School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China. FAU - Dai, Li-Ping AU - Dai LP AD - Department of Pathology, Dali Bai Autonomous Prefecture People's Hospital, Dali, Yunnan, 671000, China. FAU - Yan, Chang-Bao AU - Yan CB AD - Department of Pathology, Dali Bai Autonomous Prefecture People's Hospital, Dali, Yunnan, 671000, China. FAU - Xiong, Wei AU - Xiong W AD - College of Basic Medical Sciences, Dali University, Dali, Yunnan, 671000, China. FAU - Cui, Qing-Hua AU - Cui QH AD - School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China; Key Laboratory for Biochemistry and Molecular Biology of High Education in Yunnan Province, Kunming, Yunnan, 650091, China. FAU - Yu, Hai-Jing AU - Yu HJ AD - School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China; Key Laboratory for Biochemistry and Molecular Biology of High Education in Yunnan Province, Kunming, Yunnan, 650091, China. FAU - Yu, Min AU - Yu M AD - School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China; Key Laboratory for Biochemistry and Molecular Biology of High Education in Yunnan Province, Kunming, Yunnan, 650091, China. Electronic address: yumin@ynu.edu.cn. FAU - Qin, Yang AU - Qin Y AD - Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180621 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Lactates) RN - 0 (MYC protein, human) RN - 0 (Monocarboxylic Acid Transporters) RN - 0 (Muscle Proteins) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (SLC16A4 protein, human) RN - 0 (Symporters) RN - 0 (monocarboxylate transport protein 1) RN - 33X04XA5AT (Lactic Acid) RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Adenosine Triphosphate/metabolism MH - Biological Transport/drug effects MH - Blotting, Western MH - Cell Line, Tumor MH - Glioblastoma/*metabolism/pathology MH - Glycolysis/*drug effects MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism MH - Lactates/*metabolism MH - Lactic Acid/*pharmacology MH - Monocarboxylic Acid Transporters/metabolism MH - Muscle Proteins/metabolism MH - Oxidative Phosphorylation/*drug effects MH - Proto-Oncogene Proteins c-myc/metabolism MH - Symporters/metabolism OTO - NOTNLM OT - Glioblastoma OT - Glucose deprivation OT - Lactate transport OT - Lactic acidosis OT - OXPHOS OT - U251 cells EDAT- 2018/06/22 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/06/22 06:00 PHST- 2018/06/12 00:00 [received] PHST- 2018/06/18 00:00 [accepted] PHST- 2018/06/22 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/06/22 06:00 [entrez] AID - S0006-291X(18)31404-9 [pii] AID - 10.1016/j.bbrc.2018.06.092 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2018 Sep 5;503(2):888-894. doi: 10.1016/j.bbrc.2018.06.092. Epub 2018 Jun 21.