PMID- 36077431 OWN - NLM STAT- MEDLINE DCOM- 20220912 LR - 20220913 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 17 DP - 2022 Sep 2 TI - Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells. LID - 10.3390/ijms231710037 [doi] LID - 10037 AB - Aerobic glycolysis is an emerging hallmark of many human cancers, as cancer cells are defined as a "metabolically abnormal system". Carbohydrates are metabolically reprogrammed by its metabolizing and catabolizing enzymes in such abnormal cancer cells. Normal cells acquire their energy from oxidative phosphorylation, while cancer cells acquire their energy from oxidative glycolysis, known as the "Warburg effect". Energy-metabolic differences are easily found in the growth, invasion, immune escape and anti-tumor drug resistance of cancer cells. The glycolysis pathway is carried out in multiple enzymatic steps and yields two pyruvate molecules from one glucose (Glc) molecule by orchestral reaction of enzymes. Uncontrolled glycolysis or abnormally activated glycolysis is easily observed in the metabolism of cancer cells with enhanced levels of glycolytic proteins and enzymatic activities. In the "Warburg effect", tumor cells utilize energy supplied from lactic acid-based fermentative glycolysis operated by glycolysis-specific enzymes of hexokinase (HK), keto-HK-A, Glc-6-phosphate isomerase, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase, phosphofructokinase (PFK), phosphor-Glc isomerase (PGI), fructose-bisphosphate aldolase, phosphoglycerate (PG) kinase (PGK)1, triose phosphate isomerase, PG mutase (PGAM), glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase isozyme type M2 (PKM2), pyruvate dehydrogenase (PDH), PDH kinase and lactate dehydrogenase. They are related to glycolytic flux. The key enzymes involved in glycolysis are directly linked to oncogenesis and drug resistance. Among the metabolic enzymes, PKM2, PGK1, HK, keto-HK-A and nucleoside diphosphate kinase also have protein kinase activities. Because glycolysis-generated energy is not enough, the cancer cell-favored glycolysis to produce low ATP level seems to be non-efficient for cancer growth and self-protection. Thus, the Warburg effect is still an attractive phenomenon to understand the metabolic glycolysis favored in cancer. If the basic properties of the Warburg effect, including genetic mutations and signaling shifts are considered, anti-cancer therapeutic targets can be raised. Specific therapeutics targeting metabolic enzymes in aerobic glycolysis and hypoxic microenvironments have been developed to kill tumor cells. The present review deals with the tumor-specific Warburg effect with the revisited viewpoint of recent progress. FAU - Fukushi, Abekura AU - Fukushi A AD - Department of Biological Sciences, College of Science, Sungkyunkwan University, Seoburo 2066, Suwon 16419, Korea. FAU - Kim, Hee-Do AU - Kim HD AD - Department of Biological Sciences, College of Science, Sungkyunkwan University, Seoburo 2066, Suwon 16419, Korea. FAU - Chang, Yu-Chan AU - Chang YC AUID- ORCID: 0000-0003-0474-9935 AD - Department of Biomedicine Imaging and Radiological Science, National Yang Ming Chiao Tung University, Taipei 112, Taiwan. FAU - Kim, Cheorl-Ho AU - Kim CH AUID- ORCID: 0000-0002-6323-0714 AD - Department of Biological Sciences, College of Science, Sungkyunkwan University, Seoburo 2066, Suwon 16419, Korea. AD - Samsung Advanced Institute of Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Korea. LA - eng PT - Journal Article PT - Review DEP - 20220902 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Pyruvates) RN - EC 2.7.1.1 (Hexokinase) RN - EC 2.7.1.11 (Phosphofructokinase-1) RN - EC 2.7.2.3 (Phosphoglycerate Kinase) RN - EC 5.4.2.11 (Phosphoglycerate Mutase) SB - IM MH - *Glycolysis MH - Hexokinase/metabolism MH - Humans MH - *Neoplasms/metabolism MH - Phosphofructokinase-1/metabolism MH - Phosphoglycerate Kinase/metabolism MH - Phosphoglycerate Mutase/metabolism MH - Pyruvates MH - Tumor Microenvironment PMC - PMC9456516 OTO - NOTNLM OT - Metabolic enzyme OT - Warburg's effect OT - aerobic glycolysis OT - apoptotic death OT - carbohydrate metabolic reprogramming OT - cytosolic to mitochondrial pathway determinant OT - glucose utilization OT - metabolic selectivity COIS- The authors declare no conflict of interest. EDAT- 2022/09/10 06:00 MHDA- 2022/09/14 06:00 PMCR- 2022/09/02 CRDT- 2022/09/09 01:08 PHST- 2022/07/20 00:00 [received] PHST- 2022/08/22 00:00 [revised] PHST- 2022/08/29 00:00 [accepted] PHST- 2022/09/09 01:08 [entrez] PHST- 2022/09/10 06:00 [pubmed] PHST- 2022/09/14 06:00 [medline] PHST- 2022/09/02 00:00 [pmc-release] AID - ijms231710037 [pii] AID - ijms-23-10037 [pii] AID - 10.3390/ijms231710037 [doi] PST - epublish SO - Int J Mol Sci. 2022 Sep 2;23(17):10037. doi: 10.3390/ijms231710037.